Lecture 11: Climate effects on organisms, phenology, & interactions

Basic EEB principles (and example of PETM) leads us to expect:

o Migrations (if the world is getting warmer)
o Latitudinal (Towards pole)
! As temperatures get warmer, species that faced a northern limit
because it was too cold have this limit taken off
! Animals who like the cold will migrate north as climate gets
warmer
o Altitudinal (Towards mountain tops)
! I.e animals who like the cold will migrate to the tops of mountains
as climates get warmer
o Evolutionary change
o Population dynamics incl. extinctions
o Phenological changes
! There are biological changes in response to climate change
! Changes in timing (i.e cherry blossoms in Kyoto)

Ranges of tolerance & ecological niche modeling

Assume that a species is now found in places where conditions are suitable
o Map where a species is found now
o Measure ecological conditions where to produce an envelope of
suitability
! Focus on temperature and precipitation
! Looking to see the species lower and upper thresholds to find
what kind of environment it is best suited for.
o Use GCM (Global climate models) to predict how conditions will change
o Map where conditions will be suitable in the future
! i.e. The climate is suitable for sugar maple here but where will this
envelope be in the future? Where would the combination of
temperature, precipitation and frost-free days be in he future?
Thus, predict how far the range will need to shift
Such shifts have happened routinely through geological time
Thousands of years ago, there were glaciers right where we are now and
everything that is here now got here because the glaciers retreated.
Species have some capacity to disperse
Natural changes usually slow enough for migratory abilities of organisms to allow
adjustments of ranges
And string selection can produce rapid evolutionary responses,
But anthropogenic changes can happen so fast that species may not be able to
migrate or evolve.
o Basically, humans are changing the landscape so fast that species cant
keep up.
o I.e the climate might be changing at 3x but the ability for a species to
track the climate might be 2x.

1. Pronghorn antelope: migratory grazers of open grassland

They migrate with the shifting seasons (They have a
summer range and a winter range)
In order to get from the summer range to the winter
range, they have to get through a fields of natural gas
that are under exploration
They are super fast! They are the fastest north
American mammal
They are good at this because they have evolved an
evolutionary response to predatory cats.
o One such cat is the American Cheetah:
Miracinoyx. Which have skeleton that is similar to the African Cheetah
but their mtDNA shows that it was closer to the American cougar.
o Went extinct 11,000 YBP(Years before present)
But due to human intervention, fences kill off whole herds in the winter. (They
get stuck in them). The fences are meant to prevent grazing and to fence of
areas that are under natural gas exploration.
Humans alter the landscape and thus disrupt the migration (due to climate
change) of the antelope. This changes their ability to persist in the future.
Imagine animals that find Toronto the perfect climate, in a few years, theyll have
to move north in order to be in that perfect envelope. But in order to get
there, they have to go through the 401 and other man made structures that
could prove lethal.
2. Passenger pigeon Ectopistes migratorius (Another victim of altered landscapes)
Huge nomadic flocks roamed eastern North America at time of European
settlement.
A shattering decline: from the most to absolutely nothing:
o At European settlement, 3-5 billion individuals
o ~1/3 of all NA bird individuals
o Migrating flocks 1 mile wide, 300 miles long
o In 1870s remaining flocks still darken the skies
o They had a nomadic lifestyle.
o Extinct in the wild by 1900
o 1 September 1914Martha dies at 29 in the Cincinnati zoo
o What happened?
! Organized slaughter
o Forest fragmentation from historical records, Cadiz Township,
Wisconsin.
! The pigeons were superbly adapted to the 1831 landscape but not
the 1902 landscape. They had trouble finding forests of sufficient
size because they are nut feeders

o Hunting could not have done it alone:

! Nut feeder; pigeon was so successful because it beat the
predator-avoidance strategy of oak and beech mast crops
! Colonial life-style: allee effects likely. (High reproduction rate
because of population size and/or density)
! In pre-Europeans settlement north America, there was always
mast somewhere
! But not after massive loss of forest and fragmentation
! Reminding flocks searching for shrinking remnants of forest;
hunters recruited by telegraph and railroad; no predator refuge,
no density-dependent controls on hunters (us)
People would just kill them off and railroad and telegraphs
just made it easier.
! The irony: todays landscape would probably prevent extinction in
New England
3. Pikas in the Great Basin: many small mountain ranges surrounded by desert
American Pika
o Adapted for life in high, cold mountains
o Lethal temperature ~ 27C
o As mountain tops warm up, they have no where to go but up.
Modeling species loss from sky islands with climate changes (1996)
Mammals on mountain ranges in Great Basin
Model assumptions:
o Climate warms 3C
o Habitat moves upwards 500 m
o Habitat area shrinks accordingly
! A mountain is a cone and as you go higher, the area available
shrinks
o Species lost according to habitat loss. Predict the number of species that
are supportable by a given area.

S = cAz

S = # of species
A = area available

Number
of
species in an
area in the
present
vs.
what
is
predicted.
Each dot is a
mountaintop.
You can change the area and read off the vertical axis how many will be present

Using montane Mammals to model extinctions due to global change

Cooumns are mountain ranges:

o X = persistence
o E = extinction
This is a prediction based on if the
temperature warms up and the area as you
move up the mountain and the equation from
above.
Then people went back in 2003 to see how
the predictions went.

Measuring species loss from sky islands (2003)

Resample 25 mountain ranges where pika had
been found earlier
Pikas extirpated (gone) in 7 of 25 (30%)
4. Pollinators (bumble Bees): the rocky mountain biological laboratory, Gothic GO
(Work of James Thompson)
Mean snowfall(Since 1975) = 11.1 m
o Range = 4.7 16.4 m
Graham Pykes altitudinal transects: censuses of bumble bee species (Forging
behavior in bees), 1974
o He started looking from a road and then up in elevation so see bee
species in these communities. As you move up, there are different bees
and vegetation communities etc
Pykes censuses repeated by UofT
ROP399 students, 2006 2007
o there is an elevational shift in the
triangles (Comparing the B.
apposite ) and a corresponding
shift in he other species too.
o This shows that there was a
verticle shift in the abundance of
bees
Magnitudes of upward shifts
On average, it there is shift of
200-300 m
But whats the big deal?
How important is a shift of 250 m? Recall
altitude-latitude conversion from BIO120
Roughly, 100m altitude = 300 km latitude
So ~250m shift equivalent to ~800 km
shift.
Clear indication the changing species in
response to climate change

Are these changes general?

o Mean temperature and mean rainfall and they are presented
as anomalies
o 0 on the graph means average and anything below or above
it shows how much the average changed by.
o It shows that its getting warmer but we dont see that
upward pattern in precipitation
o Temperature is rising but the precipitation doesnt have a
trend.

o Then they looked at optimal elevation

of speices(plants in this case) from
1905 to 1985 based on where they
occurred (X axis)
o Optimal elevation based on where
they occurred from 1986 2005 (Y
axis)
o Most of the points are above the one
to one line.
o This shows that the speices are all
moving up hill

What about animals?

Northern range limit has shifted on average 16.9 km
per decade
Upper altitudinal limit has shifted 11.0 m per decade
This is for N = 764 species for latitude, 1367 for
altitude (plants + animals)
Area that warm faster: more altitudinal and
latitudinal change
This is a coherent picture of species moving in
response to climate change.

Evolutionary responses to global climate change

Tracking genetic change is hard
o Ie. For fish we had to rely on a model that counted for temperature and
density
o i.e for ram we had to rely on the fate and performance of individuals
sons.
Easy solution: focus on genetic polymorphisms or mendelian traits
o Phenotype " Genotype
! If we get a carnation that is red, white or pink, we can tell
genotype because its a simple mendelian polymorphism.
! So we take a look at ladybird beetles that comes in 2 colours
Melanic dominant to orange (dark or orange where dark is
dominant)
o Dark gives a thermal advantage due to ability to
absorb heat under:
! Cold temperatures
! Low wind
! Intermittent sunshine
! High radiation
!
There was a study done in the Netherlands along a transect (moving from coast
to the interior)
Their data showed:
o Year on the left, season on
the top
o Blue = colder than average
so the menlanic form is
favoured
o Red = warmer than average
so the red(even thought he
said orange in the previous
slide) is favoured
o Starting for 1995 onwards,
it has gotten warmer so we predict the red genotype show have higher
success

1980: Colder West to East, more

melanics as you go east
o As you go more interior you
get more melanics because it
is colder there
2004: temperature gradient erased,
cline, in melanics eliminated
CO2 " warming
Warming " eliminates temperature
gradients

Change in temperatures " eliminates fitness advantage of melanics

Changes in fitness of genotypes " Evolution in response to climate warming so
the other genotype is favoured

Summary
Global climate is having significant effects on organism
o Migration
o Phenology
o Range limits
o Evolution
The data supporting anthropogenic climate change is overwhelming, as are the
data on biological response
o We are seeing a globally coherent in the distribution and timing of
organisms is response to global climate change
How hard can you push a support system: have we broken the wire?
!
!
!

Its easy to see how the ladybirds change as they have short generation times
that happen many times throughout the year, reasonable fecundity and have a
chance to keep up with climate change via evolution
But other species may not be able to keep up
So we can use basis EEB principles to predict which species may be able to keep
up with the climate change
o Things that have short generations times and reproduce a lot
! Weeds, pests, small insects (things we dont like)

Questions for your time:

! Imagine the British spitfire planes that were used for WWII.
o It had a +12 emergency boost of 300-horse power that was safe for 5
min.
o After the 5 min, the plane was done. Once the wire was broken, you
knew it was done
Why have humans found it necessary to push natural systems so hard?
If we are blowing the Earths engine, how will we know? (Theres no wire to cut
like the spitfire.)
Whose job is it to tell us?
Will anybody listen if we tell him or her we pushed too far?
Short-sightedness
Consider the concept of antagonistic pleiotropy:
o Natural selection favours alleles with short-term gain even if there are
long-term costs
o Resulting in bodies that are programmed to senesce and die
I propose, as a strong analogy:
o Human political, economic and societal processes favour polices with
short-term gains even if there are long-term costs
o The challenge: How do we change our social structures to avoid
senescence (I.e how we get energy or food to avoid this senescence)

The challenge and prospects of humans systems

Natural selection is blind; has no mechanism to take future costs into account
But the human imagination can in principle consider future consequences
o And thus change them
My generation is leaving it up to you

Lecture 12: Ecological Consequences of Genetic Variation

Focusing on how multiple alleles in focal populations effect changes in ecological
processes
Biodiversity results in resistance to environmental
perturbation and higher productivity
Shows richness before drought vs. biomass
retained after drought
Plants that had more richness before the
drought retained more richness after the
drought.
This shows that having diversity in species
allows plants more resilience
o This species diversity is associated
with functional diversity( i.e plants and
grasses, legumes that fix nitrogen)
Question:
Do genetically diverse plots support greater species diversity?
Are plant patches that are more genetically diverse able to support more insects?
Approach: Grow groups of either monocultures of polycultures of plants(eg,
Every individual is genetically the same vs. individuals with different types of
genotypes)
o Monoculture: only 1 genotype present
! Repeated for 8 separate genotypes
o Polyculture: mixture of either 4 genotypes of 8 genotypes
Measure:
o Number (&id) of herbivores
o Number (&id) of omnivores
o Number (&id) of predators
Tests
o Do more diverse plots contain greater richness or diversity of species?
o Mechanism: is this due to sampling, or interaction among genotypes?
Experiment performed at UofTs Koffler scientific reserve
More genetically diverse plan communities do support more predatory insects

Number of different species of

predators vs. number of genotypes
The graph shows that as you add
more genotypes, the predator
richness also increases

What is the mechanism?

Genotypes in mixture react additively
Genotypes in mixture interact non-additively
Additivity:
Non-Additive:
Genotypes are independent
Properties of genotype depend on surround
genotypes
Predator abundance on genotype in Abundance of predators on an genotype in
monoculture = abundance on that genotype mono culture do not predict abundance in
in polyculture
polyculture
Communities: the whole is the sum of the Communities: the whole is either greater or
parts
less than the sum of the parts
One benefit is that we can measure
This could be because genotypes may
predators in monocultures and use it
depend of surrounding genotypes
to predict predators in polyculture.
So we wouldnt be able to grow
genotypes separately like we can if it
were additive

Black circle
= observed
data
White circle
= predicted
data

If we took a plot with 4 genotypes and went out and replicated it many times
and recorded the omnivores, wed get the average
o We can create a null expectation using monocultures
o So if we grew the monocultures and then collects the number of
omnivores and then added them up to see it is against poly cultures.
We see more omnivores for plots of 4 genotypes than what we could have
predicted by adding up the separate studies from each of the 4 genotypes
o This basically means that if we separated the 4 genotypes so that each
one was grown in a different plot, then counted up the number of
predators that visited and then added it up, this number would be less

than if we counted the predators of a plot where all for genotypes were
grown together.
For 2/3 guilds (Variety of plant strategies) of insects, plants communities are
more than the sum of their parts
Genetic variation in some species can control levels of variation and biodiversity
and species richness in other members of the community
o So if you are looking into conservation, you might have to look at other
members of the communities as well.

Why is the whole > sum of the parts?

Plant genotypes differ in nutritional qualities, growth, defensive compounds,
flowering phenologies
More diverse patches: more spatial and temporal niches for insects
o Lets say there was a patch with only one genotype, once the flowering
time is over, insects would leave but if there were more genotypes with
different times, they will be more willing to stay and move from genotype
to genotype and feed off those.
Once insects find a patch, they may be more likely to stay and visit other
genotypes nearby
Solidago (goldenrod)
Approx. 130 species in 12 generation
One of eastern N. Americas most abundant wildflowers
Colonizes abandoned fields
People think it causes hay fever but they dont. In the fields, there is ragweed
(which causes hay fever) and the golden rod flowers around the time people get
hay fever. No one ever sees the ragweed so they all blame the golden rod
Rhopalomyia solidaginis
They are spiders that make galls on the plant
Galls on plant
o Tumour that it lives inside and eats from the inside out
Plant
genotypes
differ
in
their
susceptibility

to

Galled and ungalled plants: Nutrient concentrations and decomposition rates

Graphs on the left show initial
percent of carbon and nitrogen in
galled vs. ungalled plants
Insects prefers plants with more
C and N. This makes sense
because more C and N = more
nutrients.
The graphs on the right show
decomposition
o Vertical axis = % mass
remaining

galling

o Horizontal = weeks in the field

Measure weight to see decomposition. They came back every few weeks and
measured the plants for weight
o They started off at 100% and then the tissues of the plants decomposed
at different rates (Galled vs. ungalled)
o So insects choose plants first based on their nutritional properties and
then the plants decompose at different rates and they return N and C to
the soil at different rates.
o So we have different genotypes that control the initial concentration of
these elements (N and C) which influences whether or not the plants are
attacked. Then plants that are attacked (vs. not attacked) then
decompose and recycle their nutrients are different rates.
Can genetic variation affect nutrient cycling? Yes.
Chain of causation:
o Genotypes differ in their chemical properties
o Differential attack by insects
o Genotypes differ in their chemical response to attack
o Combined set of chemical differences alter decomposition and nutrient
cycling
Coyote Bush
Native to California
o Important colonizing species of grasslands and scrub ecosystems
o Facilitates the colonization of other coastal sage scrub species
o Two distinct architectural genotypes
! Erect
Tall
! Prostrate
Low ground and wide
Alternate genotypes affect: light, temperature, and litter depth
Low trees
o Reduces light that can hit the ground
o The low nature insulates the ground
temperature
o The prostrated one is sprawled on the
ground and reduces the amount of light
that soil gets.
o The prostrated trees also lead to greater
litter depth (more falling leaves because if
they were taller, the wind would have
caught the leaves and blown them away)
o The prostrated also have cooler ground temperatures because they
provide
more
shade

Which in turn affect: Biomass, % cover, and species

richness of other colonizers
What are the consequences of the above graphs?
We are looking at biomass, % cover and species
riches for native trees, exotic trees and the total.
We can see that the pattern is the same.
Biomass, % cover and species richness is always
higher for genotypes that are the erect
genotypes. And all these qualities lower for the
crawling (prostrate) trees.
This is telling us that these trends are general
o This makes sense because these plants
affect the amount of light, soil
temperature, soil nutrition (litter depth) that then affects species richness
and diversity.
o So, overall, there is more biomass, % cover and richness associated with
the erect genotype.
Can genetic variation affect other species colonization?
Chain of causation:
o Genotypes differ in their architecture
! Their growth form ( ie. Erect vs prostrate)
o Different architecture alters light, litter layer, temperature, etc.
o Differences in light, litter layer and temperature affect diversity,
abundance and biomass of colonizing species
o So we have two difference genotypes that have cascading effects on the
ecological dynamics of the area based just on structure.
Rothamsted research Station, U.K.
Experiments started in the 1850s: effects of fertilizer on hay yields
Add N, P, K, Mg
Either alone or in concert
~90 plots of land
Can examine response of communities to:
o Fertilizer, time, or both
Difference shades of green
o Boundaries of plots, different
vegetation in each plot
o Different fertilizers over the years
= different shades of green
o The different shades are different
vegetation. They grow best based

on what fertilizer was given and for how long

No hand weeding necessary
How does fertilization influence species diversity?
Horizontal axis = the different numbers of fertilizers
added.
o 0 is our control, 1 = maybe adding P, 2 =
maybe P and Mg
Just adding fertilizer has led to species loss of 1/3 in
this plot
Species diversity goes down as you add more
elements to the fertilizer
How does fertilization affect genetic diversity?
Same horizontal axis as above but in this study, they
looked at one particular species.
o They wanted to see if adding 4 elements to
the fertilizer vs. 0 would affect the genetic
diversity.
As you add more fertilizer, there is greater genetic
diversity
Genetic diversity goes up for this species
Adding more fertilizer is making species diversity go down but it is making genetic
diversity go up. What is driving this?
Why do species diversity and genetic diversity respond in opposite directions?
Fertilizer " eliminates a limiting resource of a competitively dominant spices
o i.e. the limiting resources could be N but now that we are adding lots of
N, we are getting rid of the limit for the dominant species.
Competitive dominant " eliminate weaker species
o By getting rid of weaker species, you lower species diversity because only
certain ones survive.
Elimination of weaker competitors " opens niche space for more genotypes
of the remaining species
o The weaker species may have specialized on some combination of N, P, K
and water but then we add N, P and K and these species are eliminated
by the dominant species.
o Now, this combination of N, P, and K that was special to this plant is now
available for the genotype of a focal species to specialize on.
! So as you add more and more of the N, P and K, there are more
and more combinations available for this one genotype to
specialize on.
Therefore, more elements of fertilizers = getting rid of weaker species = lower
species diversity = more fertilizer for dominant species = dominant species now
has more combinations of the fertilizer = higher genetic diversity.

Genotype of A. odoratum: more dimensions of N, P, K, and Mg to specialize on

when fewer species are present
Summary: ecological consequence of genetic variation
Traditional view
o Ecology " selection
o Genetic variation in focal species " evolutionary response
Newer view
o Ideas above and
o Genetic variation in focal species " ecological processes (i.e
temperature, species diversity, nutrient availability, light availability,
decomposition, etc.)
o We can imagine that its a feedback
! Ecology produces selection and genetic variation fuels
evolutionary response
! But because there is genetic variation, that in turn can feedback
into affecting the ultimate ecological processes that govern the
communities and systems
! So we can see these systems as interacting feedbacks instead if
discreet systems.
o Genetics variation within species will affect almost all ecological
processes:
! Distribution and abundance of other species
! Disturbance recovery
! Nutrient decomposition

Lecture 13: The Evolution of Sexual Differences & Sexual Interactions

Genes, Environment and Behaviour
Genes and environment influence phenotypes including behaviours
Natural selection shapes behaviours
Environmental effects on trait values can be described as plasticity, and these
responses can be adaptive
Plasticity is where you take one genotype and put it in two different
environments and see two different phenotypes
o Ie. An organism with a certain genotype which we grow in high nutrition
environment and it has normal growth vs. if we take that individual and
put it in a low nutrition environment and it has stunted growth
The influences of genes and environment can be visualized this plots of the
reaction norm
Natural selection shapes the reaction norm
Two classes of scientific questions
How/what?
How an individual manages to carry out and activity?
How mechanisms within an animal work to produce a particular trait?
Proximate causes
Why?
Why an animal has evolved the trait?
Ultimate causes
What is the causal relationship between the animals genes and its behavior?
Proximate explanation (mechanistic)
o a gene is expressed and produces a protein that then generates a
behaviour
Why has this behaviour evolved and how has it changed over evolutionary time?
This is the ultimate question were trying to answer
What is the hormonal basis of infanticide?
Infanticide: Male lions if they enter a new pride, they might kill off all the offspring
that was already in the pride
This is a proximate question
Why has it evolved: what is the adaptive value of infanticide to both males and females?
Ultimate question
Have you notices that bees and wasps behave oddly in the fall?
They are a little bit drunk
o What? Reaction to alcohol
o How? Feeding on over ripe fruit
o The above two questions are proximate questions
o Why? An adaptation for locating ripened fruit because this is what they
want to be able to eat.
o Broad-leaved helleborine

This flower produces alcohol in its nectar. The bees feed on it and
become drunk and start banging around on the flower. As this do
this, they get pollen on themselves
! So the production of the alcohol might be an adaptation of the
plant that facilitates pollination by the bees
All these stories are examples
! Nothing in biology makes sense except in the light of evolution -Theodosius
Dobzhansky, 1973
! If you want to understand same sort of trait or behaviour, you have to answer
the ultimate question: why has it evolved? Why is it this way and not some other
way.
!

Genetic and environmental variation

Identical twins:
o Same genetic makeup but usually, you can tell twins apart
o Even slight differences in environment lead to variation on behaviours
o But it is hard to conduct experiments on humans
! It would be nice to be able to partition the variation (what is
genetic effect on phenotype and what is environmental)
Phenotypes reflect both genetic and environmental effects

Z=G+E+GxE
Z = Phenotype
G = Genes
E = Environment
G x E = Gene by environment interaction
Genetics have an affect on phenotype, environment has an effect on phenotype and
these things can interact
The Rover-Sitter Polymorphism
! Fruit flies were used by Marla Sokolowski for her study
o These flies can be seen on the fruit in a fruit bowl where they lay eggs.
The eggs hatch to give larvae (maggots) and then they eat the fruit.
o There are two alleles of a gene that have an affect on foraging behaviour.
o Those alleles have an affect on lots of different behaviours but were
discussing forging specifically.
Within Population variation in behaviour: Rover/ sitter
polymorphism
! Polymorphism: you have more than one type in a
population (Rover vs. sitter)
o Discovered when it was noticed that
some larvae move around more in their
food dishes
Yeast is food, and is spread on agar which is a

non-food media and you have just an agar plate

Within food patches, rovers move much more than sitters
o When there is food, some proportions of the maggots move around a
lot: rovers
o Another proportion dont move much: sitters
o When there is a lot of food, rovers move around and sitters sit
Rovers and sitters move often, and for similar distances in the absence of food
o When they are placed in the agar (non food media), both the rovers and
the sitters rove around.
This means that this phenotypic difference is food driven.
Rover/Sitter polymorphism
! You can have patches for food in different area with patches of space with no
food
Rovers move much greater distances than sitters when food is patchy
This means that rovers are off food patches more often but are also more likely
to find new patches
o Rovers are more likely to find a new patch if there is not enough food in
their current patch
o But sitters eat all the food in their patch and go around the patch in
circles hoping that a new patch will emerge. Sitters are bad at finding new
patches because they dont rove around.
o So if food is scare, there might be a cost to being a sitter because they
just sit there
o If food is abundant (There is also food in the patch, no worries of
depletion), it would be more costly to be a rover because youre
spending so much time in a non- food environment.

Observed variation in the frequency of rovers and sitter larvae

! If you collect a bunch of flies, let them have
babies, collect those eggs and figure out the
phenotype of the babies, you have this
distribution of phenotypes.
o Looks at how far the larvae like to
roam and what is the frequency of
individuals with that phenotype.
! Because you have determined phenotypes,
you can do crosses with them

Genetic analysis
! Looking at path lengths (how
far do they move around.)
! Crossed sitter males with
rover females
! We see that the F1 generation
is
entirely
the
rover
phenotype
! If you do F2 crosses, you get
75% rovers and 25% sitters
! This means that we are
looking at 1 gene that has 2
alleles where the rover is the
dominant allele.
What do these forging alleles produce?
!

This gene is involved in producing PKG

PKG an enzyme involved in cell signaling
o Located in nervous system, and in the gut

Rover/sitter transgenics
!

Marla did something a little more complicated

We can insert the rover allele in sitter larvae to see if this rover allele is the
one thing that is driving this difference in behaviour
Then measure the effects of that allele on foraging

Both foraging behaviour and PKG activity in transgenic flies resembles rover type
more then sitter
!
!
!

Rover
and
sitter
are
both
homozygous for their own allele
Transgenic individuals were identical
to the sitter except they have 1 rover
allele in their genotype
Since the PKG activity is the same for

both rover and transgenic, it means that they have found the gene that confer
these different phenotypes.
Evolution by natural selection
What is needed for natural selection?

Variation in a trait (traits can be behaviour)

Variation in fitness for the trait (traits has to be associated with fitness)
Genetic basis for the trait (it needs to be inheritable)
If you have these things, you will get natural selection and evolutionary change.

Evolution of behaviour

Behaviours have great variation (i.e. forging behaviour: rover vs. sitter)
Different behaviours have different fitness (Being a sitter in an abundant food
resource vs. being a rover in a place with depleting food)
Behaviours have a genetic basis
Because of this behaviours develop in a similar way to other traits.

Phenotypes reflect both genetic and environmental effects

Z=G+E+GxE
Environmental effect on foraging
! Another experiment done in Marlas lab
Adults were deprives of food for either 4 or 24 hours
Assayed for forging behaviour in
patchy environment
What you see:
o At 4 hours: rovers
traveled ore than sitters
o At 24 hours: Both rovers
and sitters decrease their forging activity. They are reducing the cost of
traveling when they are extra hungry.
o What the rover does at 24 hours is basically the same as what the sitter
does at 4 hours.
Summary: rover - sitter story
A single major gene underlies the rover/sitter polymorphism
The rover allele is dominant to the sitter allele
Both larval and adult behaviours are effected by these alleles
Elements of the environment (e.g. food depriva7on) also effect these behaviours
Homologous genes occur in bees, mice and humans and they have similar effects.

Phenotypic plasticity: an environmental effect on the phenotype

!

Columns = genetic effect

o Rovers are not sitters
and therefore the
genes underlying them
are different
Rows = environment effect
o i.e. Depending on what
environment you put it
in, its phenotype changes.
o For example how the rovers move a lot at 4 hours when they are a little
hungry vs. how they move very little at 24 hours when they are very
hungry
o This is phenotypic plasticity (the phenotype changes even though the
genotype stays the same).
o More traits are affected by environment

We graph the information we got

o The two lines are separated.
This is the genotypic effect
o The slope of each line is the
environmental effect.
o The slope is describing plasticity

Behavioral response to predators (plasticity)

!
!
!
!

If you go to a pond with fish, there are

near shore areas that are refuges for fish.
If youre a fish and you want to eat in the
open water, it could lead to more
predators
We can look at how much time the fish
spend in the refuges.
The fish might spend more time in the
open if there were no predators and less
time in open water if there are lots of
predators (and more time in refuges).
How much time you spend in the refuge depending on environment is a plastic
trait

Morphological response to predators (plasticity): daphnia

!
!
!
!

They swim around in ponds

When they grow up in pods with
predators, they grow little helmets with
spikes (good defense against predators)
If there are no predators, they dont
grow the helmet because the helmets are
costly and its better not to have them
This difference in phenotype from the
same genotype is phenotypic plasticity

Plasticity can be dramatic

Spadefoot toad
!

There are 2 forms of toads

o Non-cannibal:
Tiny,
have
downward facing mouths and
they eat plants
o Cannibal: relatively bigger, big
mouths that point up, and they
eat meat
o These two types are so different. What is producing this?
! The abundance of little animal food
If there are a lot of fairy shrimp, you get the big cannibals
If you grow these creatures in area with little to no animal
food, you get the non-cannibalistic type.
The abundance of food determines which type you get
The cannibals will eat other spadefoot toads but they feed
on non-relatives

Reaction norms: Visualizing G and E

Environmental effects on trait values can be

described as plasticity
The influence of genes and environment can be
visualized with plots of the reaction norm (reaction
norm = new name for what weve been talking
about)
The lines represent reaction norms
The reaction norm describes the effect of some environmental variable on the
phenotype of a single genotype.

o Reaction norm is for 1 genotype. The graph shows reaction norms for 2
genotypes. One for rover and over for sitter.
o The slopes are pretty similar. Meaning the reaction norm is pretty similar
for the genotypes. But phenotype is different because you have the
genetic effect
Reaction norms describe the effect of an environmental variable on the
phenotype of a single genotype

It is easy to visualize the importance of genotype and environment on phenotype

with these plots
For example, the phenotype
could be horn length on a
unicorn. We have two unicorn
genotypes (blue and red). We
put
them
in
different
environments (A and B) and
we can see how the horns
grow differently in different
environments with different
genotypes.
The first graphs shows that
there is a big genetic effect.
The blue unicorns grow really big horn compared to the red but there is no
effect of the environment. Horn length is completely insensitive to whatever
environment you put it in. The slopes of the lines are 0. There is no plasticity.
The second graphic shows genetic and environmental effect where in
environment A, both genotypes make bigger horns than in environment B
You can learn a lot from reaction norms

Large genetic effects, small environmental effect

! Z=G+E

Small genetic effects, large environmental effects

! Z=G+E

Complex gene x environment interactions

! Z = G + E + GxE
The environmental effect works differently for the different
genotypes in this case. So going from environment A to B
makes unicorn horns bigger for red and smaller for blue. We
have the above cases and the effect of the environment depends on the genotype.

Evolution of reaction norms

Reaction norms are the way of describing
how the environment influences the
phenotype of a given genotype.
We see variation in reaction norms and
because there is variation, you can get
evolution of a reaction norm
Imagine we have 3 different genotypes of
daphnia and they each have a different
reaction norm
The blue one, in the presence of predators,
makes a smaller helmet (Phenotypic plasticity
because the slope is not 0 but its not
adaptive. It is doing a bad thing)
The green one, there is no phenotypic
plasticity. It is insensitive to the presence of a predator and makes the same
helmet size regardless of what environment it is in.
In the red one, there is phenotypic plasticity but its opposite of what the blue
one is (Blue = negative slope, red = positive slope). It makes a bigger helmet in
an environment where there are more predators and this is adaptive plasticity.
If you put these in a pond with lots of predators, youll see that the blue and
green ones do poorly and the red ones respond in an adaptive way in the
presence of the predator so they are the ones that do well and proliferate.
We lose the green and blue genotypes and this is evolution in action.
Genetic variation and evolution of reaction norms
Daphnia tends to display phototactic behaviour
o They are attracted to or repelled by light
o They have little limb like things that funnel food into their faces. We can
look at this behaviour, their phototaxis (attraction to light, movement
towards and away from light).
o Since they eat algae and an alga grows in the light, they sometimes go
towards the light but there are also predators in the light so they can also
be repelled by light (they know the predators might be there).
o Genotypes can easily be isolated
! They reproduce asexually so you can catch one and it will
reproduce and create exact copies of itself. You can then takes
those individuals and put them in different environments and see
the effect on the phenotype.
o Phototaxis can be quantified in the lab
Food is in the light, but fish (visual predators) are too
o Assayed 10 genotypes from each of 3 lakes (1 pond that had lots of
predators, 1 that had some and 1 that had none) (G)
o They then put the daphnia in a tube, shine a light and see what they do.
Do they move towards or away from the light.
o The lakes had different selection histories (predators; many, few or none)

o Tested with and without fish smell (E)

! They tested with the cue of a predator, which was fish smells.
! Take water from a tank full of fish and put it into the tube with
daphnia, the smell tells the daphnia that there is a predator
around. Then shine a light and see which way the daphnia goes.
In the case where the
daphnia came from a pond
with many predators,
normally they are attracted
to the light but when put
in the fish water, they are
really repelled by the light.
This is because they
associate the light and
smell with predators.
In the case where the
daphnia came from a pond
with no predators, there is no response to the smell of the fish. They are not
used to smelling fish. They dont know what the smell of fish means so they
move slightly towards the light in all cases. They dont change their behaviour in
the presence of the fish cues.
The daphnia that grew up in the case of some predators had an intermediate
effect. They had a slight change in behaviour when given the fish cue but its not
as drastic as the daphnia that grew up with many predators. .
Daphnia populations with a selective history of predation risk have evolved to
avoid habitats with high risks of predation
o Basically, the difference environments and different selective historys of
daphnia in different lakes give rise to different reaction norms.
o So if you took the daphnia from the little to no predator lakes and put
them in the lake with lots of predators, they are most likely going to die
off
This has happened through the evolution of a reaction norm
o The evolution of reaction norms towards adaptive plasticity (The daphnia
that go away from light when given fish cues)
Summary
Genes and environment influence phenotypes including behaviours
Natural selection shapes behaviours
Environmental effects on trait values can be described as plasticity, and these
responses can be adaptive (and also not adaptive)
The influence of genes and environment can be visualized with plots of the
reaction norm
Natural selection shapes the reaction norm

Lecture 14: Sexual difference & Sexual Selection

How different are the sexes and why?

A lot of species have drab females and elaborate males

humans look pretty similar but they have drastic differences in their genes
o Same autosome but the difference is that males and females express
these genes differently

About 90% of genes are shared between males and females, but

Gene expression of shared genes in most tissues differs between the sexes
This is most evident in the gonads
But also in most other tissues (e.g., liver, brain)
50-90% of all genes in he fly genome (~13000) are expressed differently in the
sexes (Not just gonads)

The evolution of sexual differences (Dimorphisms)

The puzzle of conspicuous ornaments

Darwins answer (hypothesis)
Origin of sexual difference
Male-male competition

Sexual dimorphism: conspicuous ornaments

Why do we care about these differences?

o We like to know about diversity
o A lot of the differences we see between species derive between the
difference between males and females
Frigate bird
Widow birds
o The females of the birds look similar and it is hard to tell all the species
of these widow birds apart
o But the males have different colorings etc so you could tell them apart
Therefore there isnt much diversity in the females for closely related species so
the diversity in the species level is driven by the differences between males and
females in each species.

Sexual dimorphism: conspicuous behaviours

Greater sage-grouse
o They gather on leks (groups of males that are trying to attract females)
o The male has sacks that he inflates and dances around to try and attract
the female.
o One or two males end up attracting most of the females so there is a lot
of varation in the success across males with these behaviours

Sexual dimorphism: armaments

Male-male competition
Things like antlers in elks.
There are beetles where the males have longer eyes than females and they look
at other males to see who has longer eyes.
Seals battle for space on the beach

Peacock displays: Survival of the fittest?

Males have the beautiful set of feathers and the females are boring and bland
What puzzled Darwin was that since natural selection was about survival of the
fittest, it doesnt make sense to have the trait for beautiful feather. It doesnt
help with survival. Its big and bright so it would attract predators and it must be
heavy so it would make it hard to get away from predators.
His theory was that though the tail has negative effects on survival, it has positive
effects on mating success. So the success of mating balances out the cost of the
lack of survivorship.
This is an example of trade offs

Sexual selection

Sense of beauty
Females dont pick males because they are Beautiful. They pick traits that have
an evolutionary advantage to them

Sexual selection

... depends on the advantage which certain individuals have over other
individuals of the same sex and species, in exclusive relation to reproduction.
Charles Darwin
Sexually selected traits function to enhance mating success
It is a subset of natural selection but it can be useful to consider them separately

What were adding to this is that

sexual selection refers to the
number of mates you have access
to

Fitness in Males & Females

Females
o Reproductive rate = number of
eggs produced in a given unit of
time
o And then how long do you survive
to be producing eggs at that rate
Males
o Survival matters and mating success (How much access do they have to
the eggs the females are producing)

The origin of sexual differences

Why sexual selection?

o Females produce a huge resource rich egg and males produce a tiny
capsule of DNA with a motor at the end. This is the beginning of sexual
selection.
o This is Anisogamy
! Unequal-sized gametes
o We define sex by the gametes

Anisogamy

Sperm
o Inexpensive
o Many small
o Only DNA with a motor

Egg
o Resource-rich
o Few (Because they are so
resource rich, only a few
can be made)
o Large

Parental investment theory

Robert Triversv(1972):
Sexes differ in their reproductive investment
o Since the different sexes have different investment in their gamtes
Every offspring has a mother and father
Members of the sex that invest little in offspring will compete among
themselves to mate with members of the sex that invest more in offspring

Differences in the sexes

Males

Tiny, mobile gametes (sperm)

Fittness limited by access to
fertilizable gametes
Competition among males for
mates

Females

Large, resource-rich
gametes(eggs)
Fitness limited by access to
resources
Choosing among males for mates

Since there is a ton of sperm, males compete for the eggs that are resource rich
and hard to come by
Females on the other hand get to choose their mate because their eggs are
limited by resources available and not the amount of sperm available.
So we have 2 types of sexual selection
o intrasexual
! Competition between males- males
o Intersexual
! Interaction between males and females
Based on what we learned so far, it seems as though the parents invest in their
offspring at the gamete level but thats not true. There is a lot of investment that
happens after fertilization

Males limited by access to females

For males: Purple line

o You can limit the number of
mates males have access to
and you can ask how many
offspring they produce.
o So based on the above, the
more eggs you give access too,
the more fertilization that will
happen.
o Basically, males who mate a lot
and have a lot of babies will
have high fitness and males
that dont have a lot of babies and dont mate as much will have low
fitness.
For females: Green line
o Females dont need sperm so at some point, having access to more males
wont matter so we get that bend in the graph.
o At this point onwards, there is no variation in fitness and it wont matter
how many males she has access to, her fitness wont change.
o There is weak selection on females for mating success.

A Test: Bateman Curves

Batemen took fruit flies

and let them mate
between 1-3 members of
the opposite sex and asked
how did it affect their
fitness.
And just like what we
discussed above, males

with more mates will have more offspring and higher fitness.
But females still have similar numbers of offspring even if they have more
mates because in the first mating, they had enough sperm to fertilize all their
eggs,

Comparison of maximum number of offspring produced during lifetime

Given that there is this strong selection on males for mating success, you can get
a lot of variation in males
based on their mating success.
This shows you the maximumrecorded offspring for a
species.
o i.e. 1 elephant seal
male had 100 kids and
1 elephant seal female
had 8 kids. This means
that there are a lot of males in the population that are not having kids at
all.
The gull has a similar number of kids because they mate for life.
For humans, a man in the 1700s called Ishmael The bloodthirsty had those kids
o And the female had 69 kids from 27 difference pregnancies (twins,
triplets etc.)
The point here is that there is a ton of room for variation in number of offsprinf
produced by males

Sexual selection

Intrasexual selection
o Male-male competition
Intersexual selection
o Female choice

Intersexual selection: Male-male competition

Forms:
o Pre-copulatory
! # of copulation
! Number of mates a male has access to
o Post-copulatory
! Success of copulations (Sperm competition)
! Females mate multiple times and they have sperm from all of
them in their reproductive tract so there is competition between
sperm for the eggs.
! Or there is behavior from the males that determine the success
of their sperm

Manifestations of male-male competition

Fighting behaviour
o Males fighting to get access to females
Territoriality
Social status
o Walrus
o High ranking male gets all or most copulations
! Males and females hangout in herds and the males establish
dominance and hierarchy and the females just eat and hangout
! When it is time to mate, the females get on ice flows in groups
and the males come in order of dominance and dance around and
sing to them. Then the females get to choose. The dominant
males get most of the mating.
o Elephant seals
! The one who fight witch each
other for beach area. The males
police the beach and then females
come along and have kids on the
beach. Then the males have access
to all the females on the beach
again because it is his beach.
! There is a ton of variation the
number of kids the males father. This graph shows ranking and the
number of females inseminated. 1 being the best = most number
of females inseminated. If you have a good beach, you end up
getting a lot of females and thus more kids.
! And ten there are males at the bottom with little success and bad
beaches who dont have many kids
! There is a lot of selection on dominance because it affects
breeding success. The variation in fitness is high which leads to
really strong selection on dominance.
Sperm competition (Post-copulatory)
o Mate guarding
! Birds fly in pairs sometimes when they have just mated and the
males is guarding the female.
! Mate guarding in dragon & damselflies
The males grass the female below the head while she is
laying her eggs. So basically, the males hold on to the
female and they fly around like that until she lays the eggs
that he had fertilized.
! Some species of crustaceans, the females can only be mated when
they have molted. So the male will guard her until her shell has
molted, inseminate her and then guard her some more until her
shell hardens up again and no other male can inseminate her

o Sperm removal
! Sperm removal in damselflies
Have an inflatable organ with
weapons on it which is used t
get sperm of other males out
of the female
o
o
o
o
o

Copulation duration
Sperm plugs
Traumatic insemination
Anti-aphrodisiacs
Other

Alternate reproductive Strategies & Satellite and Sneaker Males

Bluegill sunfish
o Fertilization is external. Fish rub their bellies together whole releasing
sperm and eggs and the fertilization happens in the water
o Makes make a nest and encourages the female to join him and then he
guards the nest and eggs
o The male matures to be big while the female remains small
o There is 2 other strategies called cuckolder male strategies (Note, these
males mature earlier but are smaller than normal males)
! Satellite
Female mimic and tries
to convince the big
male that he is a female
so he goes into the
nest where the females
are and fertilizers her
eggs
! Sneaker
The males are so small
that they hide in the
weeds and shoot some sperm over the eggs when the eggs
are being released. They are too small to fool males into
thinking they are female
o Why so many variations? Isnt there one that is better?

Alternative Male Reproductive Strategies & Frequency Dependent Selection

Rock-paper-scissors Game in Nature

o 3 male strategies in side-blotched
lizards
! Orange, blue and yellow
o These strategies have a genetic
basis

o They vary in frequency over time

! One year, there may be a lot of blue, a few years later, it might be
mostly yellow then years after, it might be orange
Side-Blotched Lizard Strategies

Orange
o Defend large territories
o Extremely aggressive towards all males
o Access to lots of females
Blue
o Defend smaller territories
o Detect and root-out yellow males
! Good at finding yellow males and kicking them out
o Occupy smaller territory where they focus on 1 or 2 females
Yellow
o Sneaker male (on orange males)
o Mimic throat colour and behaviour of receptive females
o Sneak in the orange males territory and
mate with females

Rock-paper-scissors Game

Orange
o Attack and defeat blue
Blue
o Detect and defeat yellow
Yellow
o Female mimicry fools oranges

Prediction:

Success of each strategy in obtaining copulations dependent on frequency of

other strategies in the population

If blue is high, orange will increase

If orange high, yellow will increase
If yellow high, blue will increase

Results

Blue numerically dominated in 1991

o But with lots of blues around, oranges can invade and kick the blues off
Orange beings increasing at the expense of blue in 1992
o But now yellow males can sneak into the orange males territory and
mate, therefore there will be more yellow offspring
Yellow begins reducing orange by 1994
o But blue can kick out yellow
Blue returns to numerical dominance 1995
Suggestive of dynamic rock-paper-scissors game, where selection is frequency
dependent
o The success of one strategy depends on the frequency of the other
strategies

Lecture 15: Sexual selection & female choice

Satin bowerbird
During mating season, the males build structures called bowers
Males might steal other males decorations from their bowers because they are
so competitive.
Males try to entice the female to go inside the bower and then they mate
Sage grouse
Leks
Males do the weird behaviours and 1 or 2 of the males get almost all of the
mating.
o Huge variance in mating success
In both the bowerbirds and the grouse, the males are doing something (building or
dancing) in order to attract the female. Then the female decides if she likes those things
or not.
Female choice
Introduction to the problem
Examples of female choice in action
The benefit of female choice (direct and indirect benefits)
Why do they choose arbitrary traits?
Summary
Female choice
Any female trait (behaviour, morphology) that biases the mating success of males
toward the preferred type
We will use mating bias, female preference, female choice to mean the same
thing
No implied sense of beauty (we are talking about beauty in the evolutionary
sense)
Male choice is simply the reverse
Visual stimulation
Scorpionfly
Barn swallow
Long-tailed
widowbird
Satin bower bird
Cichlid fish
Field cricket
Jungle fowl
Tactile stimulation
Sierra dome
spider
Acoustical stimulation
Field cricket

Woodhouses
toad
Great reed
warbler
Tungara frog
Olfactory stimulation
Mouse
Cockroach
Moth

Female choice
Why do we care?
o It produces crazy traits in males
o Seems like the females are choosing based on the colour patterns, dances
and traits but we cant know that just by looking. It could be that the
females are making their choice based on something that is correlated
with these traits
Widow bird
Males defend territories and females come and build nest in the territory if they
like the male.
Tail manipulation experiment (Long tailed-widow birds)
Question:
o Are long tails preferred by females?
Experiment:
o Manipulate tail length (its like getting a hair cut so dont worry)
Experiment
Natural tail length (N)
Reduced tail length (R)
Elogatdd tail length (L)
Sham surgery (S)
o We cut off their tail but glued it back on just so we can rule out that the
cutting had an affect on anything.
Predictions:
L>N>R
N=S
Results
Before any cutting is done, these were the
results of the males across the different groups.
What we assume is that R will do worse, N and
S will stay the same and L will do better

The predictions turned out to be true

Shorter tailed males lost nests in their territory
and longer tailed males gained nests in their
territory.

Female widow bird prefer longer tails

Female preference of eyespots in peacock tails

There is a correlation between the number of eyespots a peacock has vs. how
many mates it gets. So it appears that females prefer to mates with males that
have lots of eyespots on their tails.
o But it might be just that males with bigger tails have
more eyespots and the females actually prefer the
bigger tails as opposed to males with more eyespots.
Experiment 1: Reduction of eye spot number
o Idea being that if you cut off eyespots, you reduce
mating success
o Females prefer more eyespots
Experiment 2: alter eye spot colour
o She took black stickers and white stickers and
put them on the eyespots of some males and she
left other males normal.
o We assume females like eyespot but wanted to
see if they prefer colour.
o What we saw was that males with the white and
black stickers got 0 mates. They seem to be
picking males based on how many eyespots they
have AND the colour

Female Preference of Complex Calls in Tungara Frog

Males make complex calls which is supposed to attract females to the pond and
the females then decide who to mate with
We want to know if this is the trait the females are actually choosing
You can record the sounds and play them back to the females to see how they
respond
Females Prefer complex calls
Whining brings all the girls to the pond
Then he chucking helps the females discriminate
between the males.
Females like when males put multiple chucks in
their call. (When it is more complex)
But if females prefer these traits, why dont all
males have complex calls?
o Female choices drive these traits forward
BUT natural selection drive these traits
back because of cost.
o I.e. In peacocks, more spots = predators
can see you and attack
Frog eating bat

o Whatever attracts the females to the pond, attracts the predators to the
pond
o Bats prefer complex calls too!

The problem of Female Choice

Why are male elaborations common?
o Females prefer them
o Therefore selection for elaboration
Why do females prefer certain traits?
o One of the biggest problems in evolutionary ecology
o I.e in Bowerbirds, she only gets sperm from the male so why does she
prefer what she likes?
Hypotheses for female Choice (non-exclusive)
o Direct benefits: involved direct natural selection on female. Females produce
more offspring
o If a female had a choice between a male with lots of resources vs. a male
with little resources, she will pick the male with more resources because
then she can use them to make more babies.
o Indirect benefits: Involve genetic benefits to her offspring. Females off spring are
of higher genetic quality. (More fit)
o She doesnt benefit directly but she children will end up being better. She
makes better babies instead of more, who will then make good babies of
their own and increase her fitness.
Hypotheses for female choice
Direct benefits
o Females preferences are side effects of other forces shaping female
behaviour
o Selection of resources (PI) rather than male attributes
o Male trait is indicator (or badge) of parental investment (PI)
! The traits is just an indicator of the extent in which the male will
invest in her offspring.
Female preference for males with resources
Mormon cricket
o Nutritious spermataphores (sperm, protein)
o Gelatinous blob of protein and sperm.
o The males attaches it to a female who then eats the protein and the
sperm fertilizes her eggs
o The female is trading off fertilization with getting the resource blobs and
then she can use the resources into making more offspring
o This is a direct benefit of choosing a male with a big blob
Hanging fly

o Males go hunting and bring back and show off their prey to the females
o The females are choosing based on the quality of the resources the males
are displaying
o When the female eats the resource, the male will then mate with the
female
Result
This show the fitness consequences of the choice
X axis = size of prey the male is displaying
Y axis = How long the female is willing to let the male mate with her
Females prefer males who bring big prey
So the more time he gets with her, the more sperm he can transfer and the
more offspring she will have
o There is a direct benefit to picking the big prey
o
o
o
o
o

Selection for Male Traits as Indicators of PI or Other Direct Benefits

Territory quality
o Seals that guard the beaches:
! Some beaches are good for pups and others are not. The seals
provide a good place to have and raise babies.
Parental care
Defense
Lack of parasites (STIs)
o If youre sick, your traits are bad.
o Strong, beautiful traits are a sign of health

Hypotheses for Female Choice

Indirect Benefits
o Females prefer male traits that indicate high genetic quality (good genes)?
o If so, offspring from mating with preferred males should have higher
fitness
o This happens when the only thing the males gives to the female is sperm
o Females make a choice because she will get better quality offspring based
on the quality of the sperm
o To test this, we get the females to show us who the better quality males
are, then randomly mate them and see where the better quality offspring
are.

Peacock display size is an indicator of good genes?

o So we know females like (lots of colourful eyespots)
o We can let them mate and see the quality of the offspring
o How well do they survive up to 2
years?
Preference for good genes
Males with more eyespots have offspring
that live longer
o The eyespots are an indication of the quality
of the male
o Females get better quality children from
picking males with more eyespots
o

Parental Investment (PI) Theory

Robert Trivers (1972):
o Sexes differ in their reproductive investment
o Members of the sex that invest little in offspring will compete among
themselves to mate with members of the sex that invest more in
offspring
o We know the idea that females make bigger gametes and they invest
more into their offspring that males who produce smaller gametes.
o But this is not always true
! i.e. Human males
o There are also cases where after the gametes are fertilized, the male
invests a lot in the offspring and then the sex roles are reversed
o Now since males invest more, males will be the choosy sex and females
will compete for access to those males resources (the resources is the
parental investment)
Expectations and examples
High male PI
Male choice

Giant water bugs

Pipefish

Katydids
Spotted sand piper

Plover
others

Female/female competition

Pipefish
Look like weeds and they sit in them

Pipefish Sex Roles and Mating System

Male reproductive success limited by size of their brood pouch
Female reproductive success limited by access to males
o because she needs to put her eggs in the pouch
Females compete for access to males
Females are limited by access to those brood pouches But males want the best
females with the most eggs and the highest fecundity so the males get to be
picky
Therefore females may have ornamentations that will allow them to attract the
males
Sexual selection on female size and ornamentation
Sexual dimorphism in pipefish

The male is weedy looking

The female is colourful with a colourful flap on
her back

Experimental Evidence of Sex Role Reversal

Question:
Do males exercise mate choice?
Prediction:
Males will prefer large highly fecund females
Results
The pipefish will choose the larger female
Female reproductive success is limited by male choice
Males also choose females with larger flaps on their back
The roles are revered in this case because the investment made by the two
sexes have been reversed

Relative PI and Flexible Sex Roles in Katydids

Case where males transfer the spermataphores and the females are choosing
based on the resource blob
Imagine a world where there were lots of resources, enough for everyone

o The females ability to make eggs is the limiting factor here. So in this
case the female can e choosy
As ambient resource levels decline (reduce the resources):
o No place to get resources except from males
o Male availability declines (resource limited)
o Female need for male resources increases
o Then males get to be the choosy sex
o We have flipped sex roles by altering the resources in the environment
Predictions at low resources:
o Male choice of females
o Female-female competition
In a low resource environment, it is costly to make the spermataphores and it
may take a long time to make them

Results: sex role reversal

Calling males
Mating per
female
Male choice
Female
competition

Food abundant
High because they want females
who already have food
Lower because females dont need
a lot of male. 1 make is enough so
they dont need to mate
frequently
Low because females are the ones
being choosy
No need for competition

So, what about sexual selection in humans?

o We are more attracted to symmetric faces
Mate Choice in Mice and Humans: the MHC
What is MHC?

Food scarce
Resources are hard to get so they
dont call as much.
They need recourses and they only
way they get it is from mating with
males.
Males get to choose because the
resources are scarce. The make is
the limiting resource
Competition for resources

o Major Histocompatibility Complex

o Called HLA in humans
o MHC loci code for the antigen recognition system of the immune
response
o Lots of genetic variation at MHC loci is GOOD
! Means you can recognize a lot of antigens and pathogens which is
good for defence
Do mice choose mates based on MHC?
Reasons why such mate choice might evolve:
o To avoid inbreeding
! If I matte with someone with a different MHC type, it ensures Im
not related to them
o To increase the genetic variation at MHC loci in their offspring
House mice prefer to mate with individuals of a different MHC-type
Mate choice is based on differences in
odour that correspond with
differences in MHC.
This shows that in terms of partner
selection, the mice prefer mates with
a different MHC
They choose via smell

Do humans choose mates based on MHC?

Reasons why such mate choice might evolve?
o To avoid inbreeding
o To increase the genetic variation at MHC loci in their offspring
How do we test this?
Give males t-shirts to wear for a few nights in a row then put them in bags so
we took just the smell of the male and disentangled it from all the other factors
Then females get to smell the bag and get to decide how attractive they think
the male is
Results
In the left graph, females were asked how intense was the smell and regardless of
the MHC type (same or different
from the female), the intensity
was the same
The right graph shows
attractiveness and females

preferred males with different MHC types than themselves

So it seems like female choice is mediated through these smells which is
correlated in the MHC types
All of these women were NOT taking birth control pills
The pill simulates hormonal levels present during pregnancy
And pregnancy changes the attractiveness to different smells
Perhaps women who ARE taking the pill have a different preference (e.g., nesting
response in mice)

Females on birth control

No difference in the
intensity
Women on the pill
tended to prefer
similar MHC types!!
This might be because
the pill mimics
pregnancy and changed
the attractiveness to
smells
And a pregnant woman might be more attracted to a more similar smell to her
own because her baby would have a similar smell and she is attracted to her
baby
Consider the implications this has for choosing a mate while you are using the
pill and then going off the pill (!!)

Lecture 16: Social Behaviour

Alarm calls
Ground square
Meerkat
They stand out in the environment, look out for predators and they make a call
if one is spotted
And if youre a little meerkat, standing there is a cost because you become very
visible to predators but the rest of your group can hear it and run away
This is an action that is harmful to the individual but benefice to the group. This
goes against everything weve learned so far.
Cooperative breeding
Scrub jays will help raise other babies in the nest, whoevers nest it is.
They are lowering their own fitness to raise the fitness of some other scrub jay
Eusociality
3 thinks make a group eusocial
o Overlapping generations in a group
o Cooperative breeding
o Division of labour
! Bees, ants etc.
Why would individuals forgo reproduction to help raise the young of others?
Social Behaviour
Definitions
Game theory
Evolutionary explanations of cooperative behaviour
o Reciprocity
o Group selection
o Kin selection
Social Behaviour
The interaction with and responses to other individuals of the same species
o Altruistic:
! Behaviour increases another individuals reproductive success at a
cost to ones own reproductive success
o Cooperative:
! Behaviour that, if adopted by two (or more) individuals, benefits
both
Cooperation and Natural Selection
... a special difficulty, which at first appeared to me insuperable, and actually fatal
to my theory - Charles Darwin 1859
o The idea what an individual will risk themselves and their fitness to help
others was fatal to his theory of natural selection
How then can cooperative genotypes spread in an environment of selfish genes?

Game Theory
Developed during the Cold War by John Nash to win the nuclear war with
Russia
o Economics
o Evolutionary biology
! We use game theory to explain social be bhaviours
Explanation of Game Theory
Some number of players
Set of possible strategies
Some pay-off schedule for playing A against B for all A and B
o Same pay off every time A plays against B
Hawk - Dove Game
Assume contest between two individuals over obtaining a resource
Two strategies that can be used:
o Hawk (fight aggressively)
o Dove (resolve contest peacefully)
Hawk/Dove Game
John Maynard smith came up with this strategy
2 players
2 strategies/player
Pay off matrix
R = Reward = resource they want
C = Cost of fighting = damage to you
Which strategy will prevail?
The y Axis is the pay off for playing
Dove or Hawk and the x-axis is when
they play against a dove or a hawk.
Dove vs. Dove
o They resolved peacefully and
half the time, 1 of the doves
gets and the other half of the
time, the other dove gets the
reward. So On average, the Doves get half the resource of they share it.
o Therefore if youre a dove playing against a Dove, your reward = R/2
Dove vs. Hawk and Hawk vs. Dove
o Dove is in trouble because the Hawk is aggressive so the Hawk gets the
full reward and the dove gets nothing
o The payoff is 0 if youre a Dove playing a Hawk
o The pay off is R if youre a Hawk playing a dove
Hawk vs. Hawk
o Once again, you will share the resources because you both fight
aggressively but there is a cost to fighting so you lose out on that
o Therefore the payoff for playing a hawk when you are a hawk is R/2 C

Therefore, who will win depends on who you play against and the environment
youre in

Suppose R > 2C; e.g., R=6, C=2

In this case, the getting the
resource is greater than twice the
cost
You just do the algebra from the
chart above and get your answer
So if you look down the Chart, if
youre playing against a dove,
youll want to pick Hawk because
6> 3 and if youre playing against a
hawk, youll also want to play a
hawk because 1> 0
It is always best to play Hawk!
Suppose R < 2C; e.g., R=2, C=6
Flipped scenario
o Cost is 2 times more than the
resource
If youre playing against a Dove, play
Hawk (2> 1)
If youre playing against a Hawk, play a
Dove ( 0 > -5 )
If Hawk is common in the area, Dove
is best strategy to play
If Dove is common in the area, Hawk
is best strategy to play
Might expect a mixture at equilibrium
Fitness is Frequency-Dependent
o The pay off of one strategy is based on the frequency of other strategies
in the population
o I.e the lizards with the different mating strategies
o There was variety because of the Frequency-Dependent selection
o You might maintain a mixed strategy in the end because it would be best
to sometimes play hawk and sometimes to play dove because we have a
mixture of both in population
Social Behaviour
Definitions
Game theory
Evolutionary explanations of cooperative behaviour
o Reciprocity
o Group selection
o Kin selection

Reciprocity
Given multiple encounters perhaps it does not pay to be selfish
o If you have one interaction against a Dove, it would pay off to be a Hawk
but if you were going to repeatedly interact with an individual, it would
be better to cooperative and have a social contract with that individual.
That way, you get half the resource and get no cost.
Can examine this possibility using Iterated Prisoners Dilemma
The prisoner Dilemma
Imagine two people Glen and Phil were in trouble for a minor crime and they
were arrested. The police then believe they are part of a bigger crime but need
one of them to squeal because they
dont have evidence. If one rats the
other out, they will be free but the
other will go to jail for 3 years. If they
both remain silent (cooperate) then
they both get 1 year (for the minor
crime). If they both tell then they
both get 2 years. In this case, not
telling is cooperating and telling is a
defect. They cannot talk to each
other and must give their choice by
themselves.
We assume they are both rational
agents and rational agents do what is
best for them selves. For the best
case, each person is better off confessing because that means they get no time in
jail. But, that depends on what the other person chooses. If the other person
decides to confess, then it is better for the first person to confess too. If the
other person remains silent, it is better for the first person to confess. In both
cases, it is better for them to confess. Individually, they both think that
confessing is the best strategy. But they both could have done better if they had
cooperated and remained silent.
Individuals who only think of themselves end up hurting themselves.
But if this happens over and over, Phil and Glen can form a social contract where
they cooperate with each other.
Evolution of Reciprocity (with repeated encounters)
Iterated Prisoners Dilemma
o Interaction happens over and over again
Best strategy is Tit for Tat
o Cooperate on the first encounter
o Copy your opponents pervious move thereafter
! If your partner cooperates in one move you cooperate in the next
move

Elements of the Tit for Tat Strategy?

Nice - start by cooperating
Retaliator stop cooperating if partner stops
Forgiving - if partner has cheated in past but changes then cooperate in the
next move
Predator Inspection
Fish swim together in big groups
It is hard for predators to have an interaction with just one
Some members will leave the group and look for predators, when they find
something that looks like one; they get closer and closer to it. It is risking its
own life for the benefit if the group
There a potential for repeated interaction (different fish goes out and check
every time) and there is potential for reciprocity
Someone tested that this predator inspection might be a Tit for Tat thing
Predator Inspection in Guppies

Two fish approaching a predator can be viewed as a an iterated prisoners

dilemma
At each point in time, each individual can:
o (a) Continue towards the predator (cooperate)
o (b) Hold back (defect)

Predator Inspection in Guppies

QUESTION:

Do guppies play Tit-for-Tat during predator inspection?

EXPERIMENT:

Examine predator inspection behaviour with cooperating and

with defecting partner. But it is hard to tell fish what to do so
we have to manipulate whether the fish is cooperating or
deflecting

Experimental Set-up

Put the Guppy in the tank with the predator but

put a mesh so the predator cant get the fish and
we ask how slowly does the fish get to the
predator?
In the cooperative set-up, the mirror is set up so the guppy sees itself and if it
moves forward, the mirror reflection move
forward too at the same rate
By changing the angle of the mirror, we can give
the idea that it is a defecting partner. As the
guppy moves forward, the reflection gets farther
away. This would be the deflecting partner
We ask, how close does the guppy get to the predator if it had a cooperating
partner vs. a deflecting partner

Results
The fish with the
cooperating mirror sees its
reflection getting closer
and closer to predator so I
moves closer too
The defecting mirror fish
doesnt really get that
close to the predator
It looks like predator
inspection is a tit for tat
thing in guppies.
Social Behaviour
Definitions
Game theory
Evolutionary explanations of cooperative behaviour
o Reciprocity
o Group selection
o Kin selection
Group selection
Imagine you have some birds that are breeding and nesting and this depletes the
resources
So why dont the birds make an agreement to make only 1 baby so there are
more resources and everyone gets equal resources
This is group selection but group selection does not work
Lets say that they do agree and each have one baby and share recourses but
then one of them has a mutation that makes them take more resources and
make more babies, then in the next generation, there will be more of these
cheater birds with that gene to take more resources.
There are cases where it does work and this is a made up example with real
biology
Crows
o Crows do the alarm call thing like the meerkats
Individual Selection on Alarm Calling

We have a population of crows where the

callers are red and the non-callers are blue
and were asking what happens when
predators come in?
Selection happens when predators come and
you get fewer callers because they get eaten.
This is what we expect would happen but
there is a slight change:

Group Selection on Calling

We have one tree with birds that interact with each other and there is another
tree where there are other birds that interaction and this is all good. Selection
happens and some of the birds from each tree gets eaten
Then at some point, all the birds get together on the group and intermingle and
mate with the birds from other trees before
going back to their trees.
So in the picture, we have a group of noncallers, a group of all callers and a group of
mixed birds. After the selection period
o In the group with no callers, most of
the population is gone because there
are no callers to warn them
o In the group of all callers, they have
high survivorship because everyone is
looking for callers so most of them
survive
o In the mixed group, the number of callers go down but the non callers
benefit from the caller
Then they all mix together and we see that as a whole, there are more callers
even though there is selection against being a caller at the individual level.
But non-caller groups are at a huge disadvantage because of the lack of callers
and these two ideas are in opposition
In the end, there are more callers in the population
Evidence for Group Selection?
Impatiens capensis
They group in dense groups and in these groups
OBSERVATIONS
Large plants outcompete small plants because they shade out the other plants
There are costs for growing big because they are investing in leaf tissue instead
of seeds
Small plants are still very common
Question:
Why dont large plants take over the population?
Hypothesis:
Groups with many large selfish plants do worse than groups with many small
cooperative plants
o The big plants will compete and shade out each other at the cost of
growing large and there is a cost to being large if youre in a group of all
large plants
o In a group of small pants, they might still out shade each other but they
dont pay the cost of being tall and thus pass on their seeds
o In a mixed group, it will be good to be large
o In a non mixed group, itll be bad to be large

Results
Red line = individuals in a mixed group
o as we predicted, large plants do
better because they shade out the
little guys
Blue line = what happens to the average
individual in groups that are not mixed (i.e
the entire group is large)
o Little guys do better because even
though they compete, they dont pay
the cost of being tall and they get to
invest in making seeds. The big plants
compete and pay the cost of being tall so they suffer.
Large individuals in well spaced groups tended to have high fitness.
Groups consisting of many small individuals tended to have high fitness.
These two effects tend to cancel one another out.
Kin Selection
Another example of individuals who sacrifice themselves for others is kin
selection
The difficulty...is lessened, or as I believe disappears, when it is remembered
that selection may be applied to the family, as well as to the individual, and thus
may gain the desired end - Charles Darwin 1859
Social Behaviour
Definitions
Game theory
Evolutionary explanations of cooperative behaviour
o Reciprocity
o Group selection
o Kin selection
Altruism directed toward a random individual
Imagine we have a gene that confers
altruistic behaviors and there are two
alleles at this locos; one that confers
Altruism and the other does not
We have this frog (Jeff) that is the
donor for the altruistic behaviour. He
has a gene that makes him behave in a
way that will help other at a cost to
himself
In the population, we have non-altruists and altruists and Jeff will help everyone
randomly, whether or not they are altruists.
In this case, only Jeff suffers a cost because he is helping at a cost to himself

Then non-altruists do best because they receive the benefit of the altruist
without ever having to do anything and the altruists are decreasing in the
population

Chimpanzees
We see a lot of altruist in the wild
Mother helping her child at a cost to herself
Altruists exist in families and groups
Its possible to find other individuals who have an altruist allele and they can
direct their behaviour to individuals who also have an altruist allele.
Help those who can help me
Those who are more likely to have the allele tend to be family members
Altruism directed toward a genetic relative
Jeff only helps those who have the same
genes as him so there is a cost to doing
this behaviour but there is also a benefit
for the behaviour.
So benefit is bigger than the cost
Altruists might do best at a genetic level
Hamiltons Rule
He said there will be some costs of this behavior, there will be benefits for the
individuals this is directed and there will be some relatedness between the
individuals
c = Cost of altruism to the actor
b = Benefit of altruism to the recipient
R = Genetic coefficient of relatedness (Probability that the recipient carries the
altruist gene)
bR > c
We expect greater altruism to be directed towards closer genetic relatives
because the closer the relative is, the more likely the relative is to carrying that
same altruistic gene
Alarm Calling In Ground Squirrels
Observation

Question
Experiment

Individuals give predator alarm calls

Callers are at high risk because they eat the grass and look
around for predators(cost)
Group benefits from warning (benefit)

Do squirrels with close relatives nearby give more calls than those
without? Alarm calling should be correlated to the relatedness of the
group members
Followed group and looked at the frequency of alarm calling and
tested their genotype to see how related they were in the
population

Results

Blue bar = no closer

relative
o Little time alarm
calling
Black bar = kids
o Lots of time alarm
calling
The altruistic behavior of
alarm calling is more
frequent when there is more close relatives near by
The allele for alarm calling exists where there are a lot of relatives so a lot of the
members of the population will also have the allele so the benefit of alarm calling
is going to confer to those who are also likely to carry the allele

I would happily give my life for 2 siblings, 4 grandchildren, or 8 cousins.- J.B.S.Haldane

Your siblings are related by 50% so 2 siblings is equal to one of you genetically.
So killing yourself to save your two sisters = killing your sisters to save yourself

Evolution by Natural Selection

Differential reproductive success of genes

Natural selection cannot favour self sacrificial genes
Natural selection can favour self sacrificial individuals
o If it increases the frequency of a gene
Favoured genes ALWAYS increase in frequency each generation

Lecture 17: Parent-Offspring Conflict

Parent-Parent Conflict
Who will care for the offspring?
Each parents hopes the other will invest more and there is a lot of potential for
conflict
Parent-Offspring and Parent-Parent Conflict
Parent-offspring (PO) conflict
Parent-parent (PP) conflict
Parent-offspring conflict over $$
You want to take more than they want to give
You are more important to yourself than you are to your parents
o They love you a lot but you are more related to yourself than you are to
your parents
Parent-offspring conflict over $$
Benefits of you having Costs of you having more:
more:
You are richer
Your sibs are poorer

And you care about the costs because you are genetically related to your siblings
o If something is good for your siblings it is good for you, weighted at 50%
o So you are about them doing well but only 50% as much as you care for
yourself
If you and your parents weigh these costs and benefits differently, then there will
be a CONFLICT

Parent-Offspring Conflict
Offspring begs for food
Parent provides the food
QUESTION 1:
How much should OFFSPRING try to acquire?
QUESTION 2:
How much should the PARENT provide?
If the answer to both of these question ends up being the same amount, there is
no conflict
The Trade-Off
Provisioning, p
We have a mother provisioning recourse to her offspring at some rate, p.
Current offspring fitness
o B(p) = fitness of current offspring

o B(p) = benefit which depends on the provisioning rate. So how big the
benefit is depends on how much of the resource is being provisioned to
the offspring.
o The benefit is in terms of the current offspring
o The fitness of the offspring goes up so the provisioning is a good thing but
there is s trade off
Number of future offspring
o C(p) = # of future offspring given up
o Cost is also in terms of the provisioning rate
o The cost here is the number of future offspring that are given up because
that mother doesnt have the resources to have future offspring.
o The more she gives to the current offspring, the less resources she has to
make new offspring
Maximize Benefit - Cost
o We want to maximize the benefits - cost from the offspring and the
parents perspective
o Were going to see if the maximization lines up or if there is conflict

Offspring (benefits - costs)

Siblings are genetically related (R=1/2)
Costs
A gene that causes an offspring to take Benefits
more resources now will reduce its
B(p) = fitness of self C(p) = # of future
own replication through future siblings
sibling given up
So the genes can replicate either
through the offspring reproducing or
through siblings of the offspring
There is a cost to losing siblings and it is weighted by . (your siblings are only
50% as important as you)
Offspring should maximize B(p) - 12 C(p)
o You feel the full benefit but feel half the cost because your siblings are
related to you by 1/2
Parent (benefits - costs)
Benefits
Costs
All offspring are genetically related to the
parent by (R=1/2)
Any offspring is worth so they care
B(p) = fitness of
C(p) = # of future
about any offspring equally
current offspring
offspring given
Parents should maximize 12 B(p) 12
up
C(p)
o They feel half the benefit fro the current offspring because they are 50%
related and they feel the cost because any future offspring would be
related by 1/2

Optimal Provisioning Rate for Offspring

The benefit curve saturates at one point because
there is a limit to a benefit
o If Im stuffing food into my kids mouth,
there is a limit to how much food I can
stuff
The cost curve is linear because anything given
to one offspring means that amount is no longer
available for another offspring
So the point where the dotted line meets the
benefit line is where the B 1/2C is maximized
Optimal Provisioning Rate for Parent
Same thing as above except the benefit is
reduced by because the parent is related to
the offspring by
We have the same cost because the parents
are related to any future offspring by
The spot where the dotted line meets the
benefit line is where 1/2B 1/2C is maximized
Optimal Provisioning Rate in CONFLICT

The optimal for the parent is further to the left

than the offspring
This means that offspring will want more than
what parents want to provision them
This is parent offspring conflict
All this boils down to the fact that the parent is
less related to the offspring than the offspring is
related to themselves
In general, we expect an evolutionary conflict between parents and offspring
over the level of care
o Sometimes you will see babies crying for food but parents wont give it to
them
This conflict can be resolved in many ways
Parent wins sometimes, Offspring wins other times and sometimes its a
compromise

Optimal Provisioning in Stitchbirds

Stitchbird parents have to pay some attention to the begging of their offspring,
but balance this with the potential for future reproduction.
o They give their babies food at a certain rate while taking into account any
future offspring

Optimal Provisioning in Stitchbirds

QUESTION:

Do parents adjust allocation of resources to current offspring based

on the potential for future offspring?

EXPERIMENT:

Examine resource provisioning to a current brood of parents who

are likely and unlikely to have a second brood in a season

Experimental Setup
Part 1. Supplement adults with carotenoids. (These are correlated with a greater
capacity to breed again.)
Part 2. Supplement offspring with carotenoids. (These are correlated with
increased intensity begging signals.)
Predictions
Part 1. Supplement adults with carotenoids
o Carotenoid - supplemented parents should care less (costs of increased
provisioning are higher).
! They care less because there is a higher cost associated with
giving more to the babies.
! This is because these birds want to have more offspring and if
they give more to the current offspring, they may have to forgo
the other offspring because of lack of resources and this is a
HUGE cost.
! The adults that werent supplemented with carotenoids, werent
likely to have a second brood so diverting more resources to the
current offspring means they arent forgoing anything.
o Part 2. Supplement offspring with carotenoids.
Carotenoid- supplemented offspring should receive increased
provisioning from parents.
Results
Carotenoid-supplementation for adults can
predict future reproduction.
This is looking specifically at how the
carotenoids effected the birds
Half the birds were given carotenoids and
70% of those birds had a second brood in the
season
>25% of the birds who didnt have the
carotenoid had a second brood later in the season
This was to show that the carotenoid increased the likelihood of an adult bird
having a second brood in the season.

Consequences from the babys

perspective.
This shows how frequently the
parents are vomiting up food for the
babies
In the control (no carotenoids to the
parents), when you give the offspring
the carotenoids, the parents increase
their provision rate
The carotenoids result in an bigger
intensity begging signal and he parents
respond to that
The supplemented adults provide a higher
provision rate overall (this could be
because the carotenoids are nutrients so
they are in better condition to provide
more for their babies), but they do not
care about the higher intensity begging of
the supplemented offspring. They do not
give more provisions.
The same patterns are visible for nest
visiting rate
Overall, we can see that the offspring can
gain more from the parents by increasing
the intensity of the signal but that is not true when there is a high cost of
diverting more resources to the offspring

Implications
The intensity of a begging signal by offspring can increase provisioning by parents
But, only when the costs of doing so are sufficiently low
Stitchbirds show plasticity in provisioning rates and in their responses to
offspring signals
Parent-Parent Conflict
Assume parents are equally related to their offspring
Who should provide care?
There is a variety when it comes to this question
o Female Care No Male Care
o Male Care No Female Care
o Anywhere in between
What is driving this variety in care?

Why dont all parents desert their offspring immediately?

Cost and Benefits of Deserting
Imagine two parents and their offspring, and one parents decides to leave and
they might feel okay about leaving because they feel like the other parent will
take care of the offspring
The seconds parent can leave and let the offspring die but it guarantees a fitness
of 0
Benefit of leaving is that
BENEFITS
COSTS
you can find a better mate
and have better offspring
Increased quantity of
Reduced quality of each
and also have more
offspring through reoffspring (e.g. lower
offspring
mating
probability of survival or
But if you leave, that may
fecundity)
reduce the quality of any
offspring that you already
have produced because youre not there caring for them. This is a problem
because those offspring are carrying your genes. You can ensure the replication
of your genes by ensuring that they survive. If you abandon, there is a cost to
you if they dont survive or reproduce well
Thought Experiment
Females who are recourses limited, might
have a number of kids and then be maxed
out because she cant have anymore kids
wont find any benefit in leaving and
finding a new mate because if she
produced all the offspring she can, she
wont be able to make anymore. The
benefit of leaving is low for the female. But for the male, as long as they are not
sperm limited, they can just leave and find a new mate and the benefit is high.
Females might be good a provisioning care so deserting would have a high cost
but males might be bad at it, so for male to leave, it wont affect the child as
much. In this case it benefits females to stay and it benefits males to leave.
We can imagine where it goes the other way around. This might happen if the
sex ratio in a population is skewed. If you
imagine a ton of males in the population and
a few females. If the female abandons her
offspring, she has a high chance of finding
another mate, where as an abandoning male
might have a really hard time finding a mate.
In some populations, it is possible that the
males are better at provisioning care (pipefish) and the females are bad at it. So if
you take away the care of the male pipefish, there is a high cost. If you take away
the female care, there is not difference because the female doesnt provide care.

Consider: a population of plovers in Turkey where male care predominates

Can we account for the pattern of predominately male care in terms of costs
and benefits?
Kentish Plover
Kentish Plover Experiments
Experiment #1 (benefits of deserting):
o Caught both parents on nest
o One parent (either mother or father) released
o Measured time of the released parent to re-mate
Reasoning:
o Low re-mating time - High benefit for deserting
o High re-mating time - Low benefit for deserting
Results: Experiment 1
Y axis show how long it takes to find a
mate.
Males took about 20 days
Females took 3 days
High benefit for females
Low benefit for males
Where the benefit is finding a new
partner to re-mate and have babies
Kentish Plover Experiments
Experiment #2 (costs of deserting):
o Manipulated the number of parents
! Male, female or both (control)
! Leave the female or the male or both to see what happens when
only one is providing care (leaving both = control)
o Measured brood survival
Reasoning:
o Low survival - high cost for deserting
o High survival - low cost for deserting
Results: Experiment 2
In the control, 85% of the offspring
survive
When you take the female away, the
survival rate doesnt change
But if you take away a male, there is a
huge change in the number of offspring
that survive
Low cost for females
High cost for males

Summary (both experiments)

Benefits high for females (females found

mates really quickly) and low for makes
Costs were high for males (Survivorship
of offspring when down when males were
taken away) and low for females
Measured costs and benefits predict male
care just as is observed
o Male care evolved in this system

Summary: Conflict
Conflicts in resource provisioning exists between parents and offspring because
of differences in gene\c relatedness
o Offspring want more for themselves (R=1) than sibs (R=0.5)
o Parents want equal amount for all offspring (R=0.5)
Conflicts in resource provisioning exists among parents because each would be
better off if the other invested more
The resolution to these conflicts (as always) depends on the relative COSTS and
BENEFITS

Lecture 18: Extended phenotypes

What is a phenotype?
The standard view:
o Genotype x Environment " Phenotype
o Environment leads to plasticity so you can have different phenotypes
depending on the environment
Any observable characteristic or trait of an organism.
This could include:
o Morphology
! These are obvious
o Physiology
o Behaviour
! Under the influence of natural selection
Extending the notion of phenotype
The phenotypic expression of a gene can exist outside the cell in which the
genes exert their immediate biochemical influence -Dawkins, 1999
o I have a gene and the consequence of that genes happens outside of my
body
Things produced by individuals
o E.g. bower building
! We learned about who females pick males based on their bower
and the male has genes to build the bower so in some sense, the
bower is the trait
! The structure is the trait and the behaviour gives rise to that trait
o Subject to genetic variation
! One bird might put blue things on their bower while the other
puts green things
o Influences fitness
! The blue might attract more females
o Could be exposed to selection
! The variation in fitness means natural selection can act on it
Things produced by several individuals
o E.g. dam building
o A gene encoding for taller dams leads, on average, to a benefit for that
gene
o And that leads to a higher frequency of that gene in the population
So far, were looking at genes that result in an inanimate object but Dawkins
believes that genes can exert influence in another individual
o I have a gene that gives rise to a trait which is expressed in another
organism
Things produced in other individuals
o Dawkins view: An animals behaviour tends to maximize the survival of
the genes for that behaviour, whether or not those genes happen to be
in the body of the particular animal performing it.
! A parasite in you will exert its gene on you

!
!
!
!
!
!

It can alter your behaviour in some way

And if the behaviour ultimately improves the fitness of the
parasite that had that gene, it will increase the frequency of the
gene
This is the extended phenotype of the parasite
The bower was the extended phenotype of the bower bird
The dam was the extended phenotype of the beaver
The host behaviour is the extended phenotype in the parasite

Parasite extended phenotypes

Three broad categories of extended phenotypes exhibited by parasites:
1. Behavioural modification
2. Morphological modification
! Parasite alters the structure of the host
3. Molecular modification
In order to facilitate parasite growth, reproduction or transmission.
1. If it is true that there is a gene in the parasite that gives rise to these
changes in the host and it improves the fitness of the parasite, this means
that the consequence improves something about the parasites fitness. Ie.
Replication or reproduction or help transmission into a new host
Behavioural modification
Increasing host risk taking & aggression
o Rabies
! Virus that attacks the central nervous system and then migrates
to the salivary gland so it is transmitted through the saliva of
infected animals
! It makes the animal drool a lot and become aggressive
o Aggression and risk taking could facilitate transmission to new or
definitive host
o Toxoplasmosis
! Protozoan parasite that affects cats and rodents
! It wants to be in a cat because it can only reproduce in a cat. So if
it finds itself in a rodent, its goal is to get into a cat.
! The cat is a definitive hose and the rat is an intermediate host
! Infected rodents dont fear cats anymore so they dont run away
! They did an experiment where they gave rats a choice of being in
cat urine soaked bed or a rabbit urine soaked bed.
The uninfected rats chose the rabbits because they were
scared but the infected rats chose the cats because they
werent scared and because they ere attracted to the smell
! This might be parasite manipulation of the rats to head towards
cats who will then eat the rats and thus get the parasite

Increasing vector biting rate, persistence

o Malaria parasites spend some time as a vector and then some time in
humans or other vertebrate hosts
! Parasites inside a host take many forms and there are two forms
in malaria that cant be transmitted and these parasite maintain
infection, then there are other forms that can be transmitted on
to mosquitoes
o Malaria infected mosquitoes bite more people per night and are more
likely to return if first feeding attempt is thwarted
o They are very persistent
o Persistence could facilitate transmission so a vector that promotes
persistence and aggressiveness could transmit better/ faster.
Modifying vector feeding preferences
o Experiment
! They put she types of people in tents. Happy unaffected people,
people with the untransmissable form of malaria (if a mosquito fed
on the person, it would not be infected) and they had people who
were infected with malaria and could transmit it.
! They let a bunch of mosquitoes go and checked who they wanted
to feed on.
! The mosquitoes headed towards the people who were infected
and had the transmissible from of the parasite.
! The parasite changes the odor of the host to attract mosquitoes
o Hosts infected with the transmissible malaria forms attract more
mosquitoes than do uninfected hosts or those infected with asexual
parasite forms
o This modification of vector behaviour (or host attractiveness) could
increase transmission to mosquitoes
Altering host microhabitat preference
o Parasitic worm infections in cockroaches
! Cockroach is an intermediate host and the rat is a definitive host.
! It wants to be inside a rodent where it will reproduce
o Normal cockroaches prefer plants
o Infected cockroaches prefer sunny areas
o Location exposes cockroaches to predation by definitive host
(transmission)
! Being in the sun allows the cockroach to be seen by rodents who
will eat the cockroach and transmission happens
Enslaver parasites and death grips
o Fungal infections in ants
o Fungus gets into the ant through spores and grows in the ant
o Ants leaves colony to die in a location
o Death location is (parasite) species-specific
! Depending on the species, the location varies (leaf, twig etc)
o The ant grabs on to the leaf or twig in a death grip before it dies
o Spores leave the body and can infect any ants nearby

o Location could facilitate fungal growth or spore release (transmission)

! The chosen location would be the best place for the fungus to
grow and that will lead to transmission to ants
Cocoon web construction
o Parasitic wasp infections of orb-weaving spiders
! The wasp lays her eggs in the back of a spider
o Larvae grow within the spider, eventually killing it
o The spiders, while infected make different webs that are basically really
strong anchors
o Special cocoon web is stronger and more durable.
o Could protect wasp pupae.
o Parasite changed the behaviour of the spider and builds a web that is
better for the parasite
Host suicide
o Hairworm infections in crickets or other insects
! They get inside the insect and grow up in there
o Adult worms are aquatic and free-living,
! Need water to reproduce
o Juveniles are parasitic
o Watery death could facilitate worm reproduction

Morphological modification
Parasite-induced mimicry
o Nematode infections in ants
! When people first saw it they thought it was a new type of ant
but it was just a normal ant with a Nematode infection (Big red
bulby thing at the end of the body that looks like a berry)
! In the bulb are nematode eggs
! Mimicry could facilitate transmission between patchily distributed
ant colonies
! A bird comes and sees the ant, think its a berry, eats the ant, and
poops out the eggs. Another ant will pick p the new eggs, bring
them to the ant colony and bring the parasite along
! The berry mimicry can facilitate transmission between two ant
colonies
o Trematode infections in snails
! Leucochloridium paradoxum
! Bird definitive host and snail intermediate host
! Bird drops parasite eggs, snail picks up egss as it is forging, the
parasite grows inside of the snail and then a bird will come along
and eat the infected snail
! Mimicry (and blurred snail vision) could facilitate transmission to
definitive host from dispreferred prey species

These are all nice stories, but...

Are these really parasite extended phenotypes?
i.e. are parasites manipulating hosts?
Three hypotheses
1. Adaptive for the parasite
a. Generates a fitness benefit to parasites that led to natural selection for
trait. 2
2. Adaptive for the host
a. Generates a fitness benefit to hosts that led to natural selection for trait.
b. If it is good for the host then it might not be good for the parasite
3. Coincidental by-product of infection
a. Could just be some natural consequence of the infection that gave rise to
a trait and wasnt selected for its benefit. It might look beneficial because
it was a by-product of the infection.
b. (But, may have beneficial side effects.)
How to find a parasite adaptation
Adaptive for the parasite
o Is there a benefit? (Is there a cost?)
! We need to quantify it
o Is the phenotype specific?
! Does it specifically benefit parasite, or are there other effects?
o What is the timing of this manipulation?
! Does it correlate with parasite development?
! As the parasite matures, the manipulation will get stronger and
stronger
o How does the strength of manipulation change?
! Does it depend on parasite growth?
! If the parasite in replicating inside a host and as the numbers
increase, the manipulation would get stronger and stronger.
o Lets revisit some of the examples
Parasite adaptation or not?
Increasing vector biting rate, persistence
o They did another tents experiment and collected mosquitoes outside of
the tents (before they were fed) and asked what proportion of the
mosquitoes had the malaria parasite
! 12% of the caught mosquitoes had the parasite
o Then they went inside the tents and caught the mosquitoes (after they
fed) and asked what proportion of these had malaria parasites?
! Even less mosquitoes had malaria after they fed
o They believed that a lot of the mosquitoes died trying to infect a host
! They were so persistent that they were smacked
o May increase transmission, but seems also to increase vector mortality
! More persistence but makes them more likely to get squashed
o Unclear. Seems likely to be a side effect of infection.

o Very weak evidence for being a parasite adaptation.

Altering host microhabitat preference
o Worms need temps below 38 to develop, growth is abnormal above 32
o Worms prefer a colder host
o But these are sun seeking hosts so it could be that the cockroaches are
moving to warmer areas to get rid of the worms
o Behavioural fever?
o Seems more likely to be a host adaptation, but would need to quantify
costs and benefits to say so definitively.
! Are they more likely to be killed by the parasite or maybe by
anything in the wild that can see them?
! Ultimately it seems like it is beneficial for the host but even that
we cant be sure of
Fungal infections in ants
o Specificity:
! Uninfected ants found in trees (canopy) (~15m), while all infected
ants found low to the ground (<1m)
! Seems like the ants pick places that is perfect for the fungus to
grow in terms of temperature and humidity.
o Experimental manipulation
! Moved infected ants to either ground or canopy
! On ground ants went missing
Even before the spores came out of the ants head, it went
missing
! In canopy abnormal growth
Fungus didnt grow properly (higher temperatures and
lower humidity)
Cocoon web construction
o If spiders that dont make crazy webs are infected, the parasite doesnt
do very well
o Phylogenetic evidence: pupae infecting related spiders are highly
vulnerable to rain
o For an experiment, they waited until the night before the spiders die,
they went in and removed the parasite which saved the spider.
! And the spider adjusts and goes back to building his normal web
o Experimental evidence: orb-weaving can be rescued
o Since the web making behavior is based on the parasite and not
something else, it is good evidence for being a parasite adaptation.
Host suicide
o HUGE cost for the host!
o Occurs in multiple arthropod species (crickets, grasshoppers, etc.)
o Experimental evidence:
! Let infected crickets choose, dry place or puddle
! Infected crickets significantly more likely to jump in water
! Rescued crickets (n=10) jumped back into the water
o Very good evidence for being a parasite adaptation.

Zombie snails
o The trait is really rather complex
o Possible issue is increased predation by non-definitive hosts (Other
animals that are not the target hosts can attack the snail)
! However, L. paradoxicum appears able to infect a wide variety of
different bird species
! They are generalists
o Good evidence for being a parasite adaptation.
o The benefits outweigh the costs
o Would be good to quantify increase in predation by birds.
! Birds are visual predators and these snails do a pulsing thing when
light is shined on them which make it visible to bird
! That means greater transmission to birds.
Adaptation of the parasite? Of the host? Non-adaptive? Who cares...theyre good
stories!
o We need to know because were prone to seeing adaptation even when
it isnt there
o We need to ask What kind of data do we need to show that selection is
acting on these genes and these genes must give rise to this trait which
confer befits to the parasite.
o Does the consequence of the infection benefit the parasite or the host?
! The answer to these will tell us when we have to treat the
infection
o Could have implications for:
! Treatment
e.g. fever and inflammation
! Control
e.g. could manipulate vector behaviour
o Plus its good to do science right.
! Dont take adaptation talk lightly!

Lecture 19: Introduction to Evolutionary Medicine and The evolution

of virulence
Introduction to Evolutionary Medicine

Medicine is about 3 different things, diagnostics, treatment and prevention

Questions in Medicine
o Diagnostics
! What is causing damage or disease?
! What functions or pathways are being disrupted?
o Treatment
! How do we interfere with the organisms or pathways that are
causing disease or damage?
! How do we repair any damage?
o Prevention
! How can we protect against the causative agents of disease?

Evolutionary Medicine
Definition:

Application of evolutionary principles to the problems of health

Approach:

Asks why (ultimate) rather than how (proximate) questions

Utility:

Better understanding = better prevention, treatment

We are products of evolution and so are pathogens so our
interactions are subject to evolution as well. So if we understand
these processes better, we can diagnose, treat and prevent better

Introduction to Evolutionary Medicine

PROXIMATE QUESTIONS
o Questions in Medicine
! What is causing damage or disease?
! What functions or pathways are being disrupted?
! How do we interfere with the organisms or pathways that are
causing disease or damage?
! How do we repair any damage?
! How can we protect against the causative agents of disease?
Evolutionary Medicine
We need to think about how we get sick and why
Diseases need both proximate explanations of underlying mechanisms as well as
ultimate explanations of why any vulnerabilities exist.
Evolutionary Medicine
Questions in Evolutionary Medicine (why questions)
o Why are we vulnerable to disease?
o Why do we age?
o Which symptoms of disease are harmful? Which are helpful?

o Is this a response (e.g. fever, resistance, virulence) adaptive, and for

whom?
! If it is adaptive for me, you wouldnt want to treat it. i.e fever that
might kill the pathogen
o When do we expect resistance to evolve?
o When do we expect the evolution of extreme virulence?
o Will vaccines lead to the evolution of pathogens?
Three reasons why we are vulnerable to disease
Tradeoffs: Structures and systems must balance conflicting demands
o i.e. DNA repair is good because it will make you healthier but it take
energy away from doing other things like making babies.
o Defenses: systems built for defense against pathogens and degradation
come at some cost.
! Its a huge metabolic cost to upkeep your immune system so
natural selection has to work with the trade offs and you e up
with defenses that are not perfect
Environmental Change: Environments change at a rate that exceeds our rate of
evolution. Then you will not be perfectly adapted in a habitat
Pathogen evolution: Pathogens evolve faster than we do.
o They have a shorter generation times and have a higher mutation rate
Virulence Evolution
Examples the problem
Conventional Wisdom
Parasite Adaptation
o explicit theory
o verbal theory (Ewald)
1918 Influenza Epidemic
March,1918a few dozen WWI recruits came down with the flu
As these soldiers were mobilized they spread the virus quickly to other soldiers
Confined and heavily populated living
quarters led to an increasing epidemic
By September1918 it had become
increasingly virulent
Between September and December
1918 thousands of otherwise healthy
young adults (20 to 45 years old) died
By 1919 about 30-50 million people
were killed
The graph shows death rate. The top
line is all death from any reason at it
is going down because of vaccines and
diseases
o The bottom line is death from infectious diseases so the drop in total
death is largely attributed to the drop in infectious diseases

The point of the graph was to show the crazy spike which was the result of the
influenza
Then this influenza virus seemed to vanish

Influenza
Most current flu viruses are not particularly virulent
The 1918 flu strain was
WHY?
Ebola virus
Causes Ebola hemorrhagic fever, a severe and often fatal disease
Spread by direct contact with contaminated material (including from dead
bodies)
High fever, headache, stomach and chest pain,
vomiting, and severe internal bleeding
In 1976 the first Ebola outbreak in humans occurred
in Zaire and Sudan (~500 cases) and then
disappeared
In 1989 Ebola appeared again in monkeys imported
into Virginia, USA
Since 1976 there have been ~25 outbreaks in Africa
The graph shows the deaths from the recent
outbreak and it way higher than any other outbreak
The typical thing about ebola is that is kills a bunch
of people who get it.
2014 West African Epidemic
As of March 8, 2015
o Guinea
! 3285 cases, 2170 deaths 66% fatality rate
o Sierra Leone
! 11619 cases, 3629 deaths 31% fatality rate
o Liberia
! 9343 cases, 4162 deaths 44% fatality rate
Basically, 41% of people who get ebola die from it. To put this into prespective,
the 1918 flu, how 30 million people died, that was only about 3%.
Ebola is extremely virulent. WHY?
Why is the common cold so benign?

Common cold is caused by the rhinovirus but it wont kill you unless you some
other underlying health issue

Virulence
The additional mortality rate that a pathogen imposes on an infected individual
(the host)
There is already some sort of underlying mortality rate in a population that this
adds to (age, being hit by a bus etc.)

It is the trait of the parasite or pathogen

Why is there variation in the level of virulence in different diseases

Conventional Wisdom
Parasites that harm their hosts thereby harm themselves
Over time the coevolution of pathogens and their host will lead to a mutualistic
association
o The parasite in like a dinner guest, you are inviting them over to eat and
it wont eat too much because it is polite. Itll eat enough so it wont
cause you damage
Instances of highly virulent pathogens are cases where the host-pathogen
relationship is recent
o There hasnt been time to let evolution make the relationship more
mutualistic
Think about Ebola. Can it fit with the conventional wisdom?
Ebola is normally hanging out in a bat and it doesnt harm the bats too much
Then the bats infect other animals like Apes and we interact with them a lot
more (bushmeat trade)
This is spill over event. Something that normally lives in a zoonautic reservoir
and then through interaction, it is introduced into the human population
Ad because humans normally dont interact with this, they do not have immunity
to it
We havent have time to evolve it is a new interaction
H5N1, Bird flu
1997, deadly outbreak of bird flu reported in Hong Kong
Subtyping: H5N1 (first seen in chickens in Scotland in 1950)
From 2003 un3l Dec 20, 2013: 694 cases confirmed, 402 deaths
Virtually every case involves close contact with birds
o Passing from chickens, ducks etc to humans. Not human to human
Case fatalities ~ 60%
These are new interactions because it is a spill over event. It is coming from
animals
Tuberculosis
Challenges the conventional wisdom
Been with us since ancient Egyptian times but it still kills many people
This is a case of an old association that is still virulent
Myxoma virus
Challenges the conventional wisdom
When Europeans colonized Australia they brought rabbits with them
The population of rabbits then exploded
In 1950 scientists released a myxoma virus into the rabbit population to kill them
and thereby control their numbers
The virus causes a disease called myxomatosis which is highly virulent

According to conventional wisdom, it should have become less virulent over

time and benign to its host
o It did become less virulent but it never reach mutualistic
levels
o So the conventional wisdom is missing something
! We decreased virulence but we reached an
intermediate level

Grandfather of evolutionary medicine

Roy Anderson
Robert May
Parasite Adaptation Hypothesis
Level of virulence is caused by parasite replication rate in host
o How bad it is depends on how much it is replicating
o The cost of replication is high virulence
Transmission rate is also caused by parasite replication rate in host
o The benefit of replicating a lot is that you might transmit a lot
o We are at a trade of
Parasite replication rate (and therefore virulence) evolves to maximize parasite
transmission and spread
o Parasites want to be transmitted so evolution will maximize transmission
Parasite generation time is very short and therefore we can consider parasite
evolution in absence of host coevolution
o Because generation time is so fast in parasites, the cost evolution is
negligible
A Simple Model for Virulence Evolution
Pathogens maximize # of new infections
T(r) x L(r)
o r = the replication rate
o T(r) = # new infections/day
! Increase replication rate (r) then you increase transmission
o L(r) = # days infection lasts
! The number of new infection you generate depends on how long
you are infected for
! You transmit at a certain rate per day but how long does that
infection last?
If you increase replication rate, you suffer the cost of virulence so if you increase
replication, you decrease the duration of infection
A trade-off between transmission and host mortality
Increased virulence increases transmission, but decreases host longevity
We get an intermediate level of replication and intermediate level of virulence so
we can optimize this
Optimizing virulence
The most virulent strains increase transmission rate, but kill the host quickly
The least virulent strains tend to be cleared by the host quickly

Prediction: strains of intermediate virulence will increase in frequency.

o They released really virulent ones that killed rabbits before it could be
transmitted
o The low virulent ones were cleared by hosts
o But the intermediate ones were perfect
The prediction was upheld in the Myxoma rabbit system.

Ewalds Theory (verbal optimization)

Trait to be optimized: Replication rate and therefore virulence. If I increase replication,
I increase virulence
Fitness:
# of new infections
Constraint:
High reproductive (transmission) rates result in high host
mortality and reduced transmission period
They want to transmit more but at the constrict of
killing their host
Modes of Disease Transmission
Mode of transmission will effect how the trade off plays out
Direct host-to-host transmission
o Like with a cold, if you had a cold and you shaking my hand and I lick my
hand, I will get sick
o Hosts must be mobile and functioning relatively well in order to transmit
disease
! I have to be healthy enough to move and cough on people and
pass it on. It has to be direct
o Prediction:
! Low replication rate and therefore low virulence
! The cost of being very virulent is very high because you need the
host to not be too sick so they can transmit the virus
o E.g., Common cold
Vector transmission (e.g., mosquitoes)
o Hosts do not need to be mobile in order to transmit disease
! Humans are less likely to swat away mosquitoes so an unhealthy,
less mobile host might be a good thing for malaria parasites
! They dont need the host to be moving around. The transmission
occurs through vectors (the mosquitoes)
o Prediction:
! Higher replication rate and therefore higher virulence
o E.g. Malaria

Virulence and modes of transmission

Ewald took parasites and
asked if they are directly
transmitted or vector
transmitted and how bad are
they
X axis, how bad they are
(what proportion result in
death to host)
Y axis how many pathogens
fall into that category
For the directly transmitted pathogens most of them have a low fatality rate as
we predicted
For vector born diseases, we have a bunch of things that are super severe killing
a lot of people and a bunch of thing sin between
This is what Ewald meant by mode of transmission is going to effect the optimal
level of virulence
Cholera
Infections caused by the bacterium Vibrio cholerae
Death via severe diarrhea and dehydration
o Can kill you really quickly
Outbreaks still occurring in some regions (e.g. sub-Saharan Africa), the last in the
USA was 1910
o After 2010 earth quake in Haiti, there was an outbreak of cholera which
is still happening
3-5 million cases per year, >100,000 deaths per year
Water acts as a vector for this and many other diseases.
o Someone who is sick might shed the infection in their feces and in a place
where water sanitization isnt perfect, the bacteria can get into the water
and someone far away might get Cholera
Diarrheal Diseases (e.g., Cholera)

This graph asks, of the cases of

diarrheal diseases, what proportion is
waterborne vs direct contact? (X
axis)
y axis = what proportion leads to
death?
This shows that infections that are
waterborne, they are nasty infections.
They lead to higher death rates
So water transmission is freeing up
the cost of being too virulent
o Because you can infect someone miles away without having the host
being mobile
o This results in much more virulent infections

What can we do to cause the evolution of lower virulence?

Remove vectors (e.g., mosquito extermination, netting in houses)
Provide uncontaminated drinking water
This idea can be generalized
Pathogens will evolve to be highly virulent when transmission between hosts is
easy
Virulence evolution: Public health implications
Since we figured out what causes high and low virulence, we can use it to put
into place measures that will direct the evolution of pathogens in our favour
We can push evolution to make pathogens less virulent
If you reduce transmission, you lower the benefit to parasites and then the cost
goes up which till lead to lower virulence in order to lower the costs
Pathogens will evolve to be highly virulent when transmission between hosts is
easy
o If we make transmission hard, we can drive the evolution of lower
virulence
o Remove or reduce vectors
! Mosquito eradication
! Mosquito netting
! Provision of clean water
o Increase basic cleanliness (health care workers, cooks)
o Decrease host densities
o Isolate patients
o Etc.

Lecture 20: Virulence Evolution II

The Evolution of Virulence II
An overview of the evolution of virulence
o The impact of multiple infections
o Accidental infections
The evolution of influenza
Summary: Virulence evolution (so far)
Conventional wisdom
o Parasites should not harm their hosts
Enlightened theory
o Parasites evolve to intermediate virulence based on a relationship
(tradeoff) between virulence and transmission
Other complicating factors
o Transmission strategy
o More things well learn about today...
Predicting optimal virulence
WE talked about how replication rates
within hosts is a pathogen trait which is
related to how well that pathogen can
transmit
And we have the saturating blue like
because at some point, you cant have
more pathogens. Youre just full of them.
This is the benefit of replicating with in a
host
The cost could be how long does the infection last
The lines are inverse of each other.
o If you replicate quickly, the infection is short
o The virulence is high and the cost is high
o If you dont replicate as much, the infection can last a long time
o Virulence is low and the cost is low
We want to maximize the benefits minus cost
We find where the difference between the two lines is the biggest
Then we say that virulence should get to this point to maximize the benefit
minus cost
Predicting optimal virulence
How does transmission mode affect
optimal virulence
Think of Direct contact vs. vector
transmission
Vector parasites can be more virulent
because their hosts wellness doesnt
matter. Vector parasites can just wait for

a mosquito to transmit the illness but something like the common cold requires
the person to be less sick so they can get up and be mobile. Vector parasites can
thus have a higher replication rate than direct contact ones. The direct contacts
optimal is lower than that of the vector
Key assumptions of theory for virulence evolution
Host population is well-mixed (no spatial structure)
o People are interacting randomly
The tradeoff involves only virulence and transmission
o Only these things and nothing else
Infected hosts cant be coinfected by other strains*
o Were looking at only 1 pathogen trait
o This one is what we shall focus on today
! For a lot of diseases this isnt true
Virulence is a function of parasite replication
These assumptions often apply to micro parasites.
Multiple infections
For some diseases, infections with
multiple strains are common
e.g., malaria infections in humans
The table here looks are different
parasites in different countries and what
proportion of the infection harbor
multiple genotypes
So for countries with malaria, multiple
infections are a rule, rather than an
exception
There are different malaria parasite genotypes in a given host at any given time
Malaria infection are often diverse with different genotypes and they get this way
by 2 means
o A single person might get bites from multiple
vectors. In places where malaria in endemic,
people get 350 infectious bites per year
o A single mosquito can harbor multiple
genotypes and transmit them to a given host
o In this picture, what they did was sequence 1
gene of malaria parasite (this is an
underestimate of diversity)
o Person 1 has 4 different strains (4 different colours) and it shows you the
frequency of the gene in the host (by how big the bar is)
o Another person has 3 strains
The idea is that multiple infections is very common
We need to think about how this might effect virulence evolution

Multiple infections
The top graph shows the single
infection that we are used to with
one intermediate optimum (black
dots)
If you add another strain (green
dot) and that strain increase its
replication rate a little bit, that
parasite gets the advantage that
comes along with increasing its
replication rate. Transmission will
increase but only the green one will
benefit because it is the one
increasing its replication rate
The cost increases too (killing the
host) and effects all the strains equally
So the benefit goes to the green
strain but the cost is for all the strains
This is the tragedy of the commons
Multiple infections & the tragedy of the commons
We rotated the graph and made it so
that transmission is a function of
virulence. We took the graph above
and rotated it so the red line is now
the x axis
We are looking at what transmission
looks like with respect to virulence
This is what the transmission curve
looks like
In a single infection, it pays to be
prudent
o You dont want to be too
virulent because itll kill your host too quickly. You get the biggest benefit
for the cost
But when you share a host, you go better by growing a little faster
You might kill the host and everyone would have done better if reduced their
growth rate a little bit, but because you gain the benefit of growing a little faster,
your competitors do worse
What matters here is the relative transmission. If you can transmit a little bit
better than the other strains and that is what natural selection is going to act on.
(The variation in transmission)
Tragedy of the commons predicts that the level of virulence for parasites that
encounter lots of mixed infections should be higher
So, theory predicts that multiple infections select for increasing virulence. Any
evidence of this? YEP!

Multiple infections select for higher virulence

Rodent malaria infections
This shows you a bunch of different genotypes
The dots represent the means from 5 different infections and were seeing what
happens to parasite
numbers over time. They
grow up, start to crash
(eating up resources and
running out) and then
different things happen
depending on the
genotype.
The red and yellow ones
are more virulent and they
cause more harm to their
hosts. The parasite densities are higher and the host is more anemic (lower red
blood cell densities)
The blue and green ones are less virulent and make the host less sick
We have a variation in virulence and then we ask, if we take the blue and green
ones and compete them against really virulent genotypes, who would win in that
competition?
Thats what happened in this study
They compared all the genotyped
relative to the focal genotype that
was very virulent
Then this graph shows
competitiveness.
What proportion of the parasites
were made up of the other
genotype that we used as a
competitor, after the infection was over.
Less virulent genotypes did poorly against the very virulent strain. Their densities
were only 10% as high as the competitor
But more virulent types made up to 50% as much density as their competitor
So what this shows is that in competition with virulent type, it is the virulent
types that do the best
Then if multiple infection happens often then there will be selection for higher
virulence because they do the best and they will be transmitted more and more.
Relative transmission is what matters
A host can be infected by several parasite strains (or even species) because of
multiple infections or rapid within-host evolution
If the strains compete for the same resource, there is a tragedy of the commons
The strain with the highest growth rate, out-competes the others in this host
Even though overall transmission is lower, the more virulent strain has higher
relative transmission

Summary: Virulence evolution

Conventional wisdom
o Parasites should not harm their hosts
Enlightened theory
o Parasites evolve to intermediate virulence based on a rela5onship
(tradeoff) between virulence and transmission
Other complicating factors
o Transmission strategy
o Within-host competition
o Accidental infections
Three Stages in the Evolution of Virulence
Pathogens crossing species boundaries
Stage 1: Accidental Infection
o Many pathogens can cause infections in novel hosts.
! Some may fail to cause secondary infection
The pathogen will die with the host
! Some may cause a short chain of infections and then quickly die
out
some people get it and then the infection dies out
! In both cases, if you put the person in isolation, it ends the
pathogen
o Accidental infections can be particularly virulent, but are not necessarily
so. Low virulence infections are probably underestimated.
o No evolutionary prediction about their virulence is possible.
! If it is new to humans, we do dont have immunity to it and we
might be very susceptible to it
! At the same time, the pathogen has never had a human host so it
hasnt adapted to us either so it may not have the tools required
to exploit us in an aggressive way
Stage 2: Virulence evolution soon after invasion
o Successful invasion requires a chain of host to host transmission.
! If it can pass on to other people, it may have had time to evolve
to better exploit its host
o Initially this will be an epidemic (a rapid increase in the number of
infected hosts).
o The invading pathogen will be poorly adapted to its host and therefore
there will be rapid evolution of the pathogen, including its virulence.
o The rabbit Myxoma story is a good example of this process.
o Ebola so far is different from everything because it was a prolonged chain
of human to human transmission, no stuttering in the chain.
o Bird flu and MERS (Obtained from camels) are example for stage 2
Stage 3: Evolution of optimal virulence
o Evolution of the pathogen will slow as adaptation occurs
! Selection wants to get to the peak of the transmission as a
function of virulence the curve and as it gets closer, evolution

slows down because selection is strong where there is very big

differences in fitness and gets weakers as we get near smaller
differences,
o Near equilibrium, a trade-off boundary will be reached
o The trade-off is between virulence and transmission (both determined by
replication rate)
o Total transmission of the infection is expected to be maximized (i.e. # of
new infections).
Evolution of Influenza
Marked annual cycle in seasonal flu outbreaks
Seasonal flu patterns in the USA
over 100 years
Flu is more common in the winter
o We spend more time
inside and people are in
higher densities and
transmission is easier
In 1918 and 1919 the graph blows
up and this was the Spanish flu
The death toll
World Health Organization estimates that flu kills 250,000 - 500,000 people each
year.
Centre for Disease Control estimates 36,000/yearin USA.
Health Canada estimates 4000-8000 people die in Canada of the flu each year.
The rage is so big because when they die, it could be because of another illness
o Influenza makes you more susceptible to other infections
Death is usually due to associated illness.
This graph shows death from influenza or
influenza like infections over the course of
several years.
The black line represents predictions
And it seems like mortality in the last 3 seasons
have been bad and death rates have spiked
These peak points show that 10% of all death is
because of flu
Immunity and the flu
Most individuals recover from the flu and are thought to maintain lifelong
immunity to that particular strain
Evidence:
o 1977 re-emergence of a genetically identical variant of a strain of H1N1,
which was last observed in 1957.
! There was a 20 year disappearance and then it came back and
people who were older than 20 were immune to it but people

who were born in the 20 years did not have immunity and caught
the infection
o Majority of illness occurred in people under the age of 20. Older
individuals retained immunity from the 50s.
Rapid evolution at several sites
Seasonal flu epidemics and past pandemics are caused by influenza A.
There are 2 surface antigens that we care about the evolution of: neuraminidase
and hemagglutinin
o We name viruses based on this i.e H1N1
NA and HA: surface proteins. Escape humoral response.
NA neuraminidase: allows escape from host cell and spread throughout body.
HA hemagglutinin: principal antigen on surface
o A principle antigen on the surface which the immune response can
recognize and attack
NS interferon antagonist: escape hosts natural immunity
PB2: point mutation in this protein responsible for virulence of 1997 Hong Kong
flu.
PB1, PA, NP: escape from cellular response.
o If youre the pathogen, you dont want the immune response to recognize
hemagglutinin so you want to change it
Evolution of the antigenic sites on the Hemagglutinin protein (HA)
Analysis of a collection of flu viruses from seasonal flu
epidemics from 1960-1987
Continuous nucleotide substitutions
Continuous rate of evolution
Most seasonal flu strains tend to go extinct
Recent flu strains are descend from a single ancestor
They looked at the rate of evolution with the x axis being
the year the sample was collected
They compared the divergence of the hemagglutinin gene
from the original sample from 1960
There was a linear progression of changes in the gene
This suggests that there is a static rate of evolution.
o It s constant and it it change the hemagglutinin little by little
Hypothesis:
Each year, the strain with the most new mutations will be best at
evading immune response and will thereby become most common
This is a collect from 12 years of strains and their relationships
across the years
Prediction:
Next years new genetic variants should be most closely related to
the strain this year that had the most new mutations
o The one that does best next year is the one that is most
different from any of the others ones this year

o So for the 12 years, you can look at each year and see which strain was
the most different (most mutations) and ask if that one is present in next
years flu season
Results:
In 9 out of 11 flu seasons this prediction was upheld
o The flue strain that caused the next seasons epidemic was the one that
was most different
Human immune response plays a strong role in determining influenza evolution
o You dont want to be common so evolution drives pathogens away from
commonality
Vaccines for influenza
We can use the information from above to make vaccines
WHO gathers information on circulating strains and epidemiological trends of
influenza in 83 countries and updates vaccines each year to best match these
data.
New strains are tested against existing vaccines to determine whether they
induce satisfactory antibody levels in human sera.
It takes about 6 months to create a vaccine
Making vaccines
You cant get sick from the flu vaccine because it is not alive. It is dead and
cannot replicate
Inactivated influenza virus vaccines are cultured in chicken eggs and produced in
proportion to the recommendations of the WHO each year
Inactivation is achieved through damage to the viral nucleic acid by chemical
treatment or radiation.
Vaccine is trivalent.
o In the vaccine you have protection against influenza B, two influenza A
strains, an H1N1 strain and an H3 strain
Vaccination against the flu
WHO suggests that young children, pregnant women, the elderly and persons
with chronic conditions/weakened immune systems should be vaccinated
o They are most susceptible
Herd immunity: vaccination of people not at high risk of influenza mortality helps
to control infection rates
o Vaccinate people who are not at risk so that they dont get it and then
transmit it to those who are a risk
o People who are in close, frequent contact with high-risk populations
should also be vaccinated.
o Appropriate for all school-aged children, health workers etc.

Many faces of the flu

Seasonal (or common) flu:
o A respiratory illness that can be transmitted person to person. Most
people have some immunity, and a vaccine is available.
Pandemic flu:
o A virulent human flu that causes a global outbreak, or pandemic, of
serious illness. Because there is little natural immunity, the disease
spreads easily from person to person. Currently, there is no pandemic
flu.
o 1918 (Spanish flu), 1957 (Asian flu), 1968 (Hong Kong flu)
Avian (or bird) flu:
o Is caused by influenza viruses that occur naturally among wild birds but
there is an occasional spill over on to humans. The H5N1 variant is
deadly to domestic fowl and can be transmitted from birds to humans.
There is no human immunity and no vaccine is available.
Evolution of the flu - generating new variants
The constant change of the hemagglutinin, evolution and mutation and the step
wise accumulation of change in the gene is antigenic drift
Most evolution in flu is brought about by the
accumulation of many small mutations (antigenic drift).
You can think of this as simple mutation.
Occasionally, major antigenic shifts (reassortment) occur
where whole RNA segments from one strain to another
are transferred. You can think of this as gene flow.
The H1N1 has segmented and cut up genome and since
it is cut up, it can swap it with other viruses that share
the same host cell and have a massive shift in the virus
because were talking about huge chucked on the
genome being transferred
How are genes transferred?
Viruses use the machinery of host cells to replicate themselves
Recombination event between two virus strains during multiple infection of a
single cell
o While they replicate, they can swap the genome pieces and create
progeny that didnt exist before.
o I.e H1N1 + H3N7 = H1N7 or H3N1
This results in the origin of a new virus strain that consisted of parts of both its
parents
The concern is that this is the way pandemic strains are generated most of the
time
They think the avian flue someone got into a human and was good at
transmitting so it didnt this massive shift to create an epidemic
So it was a little better at transmitting and then as it passed along humans it
changed via antigenic drift and not antigenic shift
But every other epidemic we know about came from this antigenic shift

o This means that a human has to have a human virus and well as a non
human virus at the same time and then those genes can be swapped
o So the non human virus can get the human transmission genes from the
human virus and become a human transmittable virus
o Or super virulent genes of the non human virus can be transferred into
the human virus
Evolution of pandemic strains
1918 Spanish Flu
1957 Asian Flu
1968 Hong Kong
20?? Avian Flu

antigenic drift of an avian flu 30 million (500,000 US)

antigenic drift (human and non-human) 70,000 US
antigenic drift (human and non-human) 34,000 US
most likely to be an antigenic shift

1918 H1N1 Pandemic

20-30% of the worlds population was infected. 30-50 million deaths
With the exception of avian viruses, almost all human influenza A cases are
descendants of the 1918 H1N1
It occurred in 3 distinct waves, and there is some
suggestion that drift occurred between waves.
o And this wasnt normal because normally
The age distribution of virulence was unusual.
o If you added up all the deaths and graphed it
o The dotted line shows that the flue normally
kills the young and the old
o But the Spanish flu had a peak in mortality in
the middle ages (12-35)
It appears to have arisen de novo from an avian
strain. It was very random
But the process of evolution within humans led to higher virulence and
transmission rates
Origin of the 1918 H1N1 variant
No evidence that the virus resulted from reassortment of an existing human
virus with another of animal origin.
The first appearance of the virus may have been as recent as 1915.
It appeared simultaneously in pigs.
Current thinking: H1N1 appears to have arisen de novo from an avian strain.
The emergence of Avian Flu and the potential for a pandemic
1997 - Avian Flu (H5N1) first appears transmitted from birds to humans, Hong
Kong
2004 - A new strain of H5N1 appears
o Some evidence of a single human to human transmission, Thailand
2006 - Several strains of H5N1, generated through reassortment are circulating
The fear is that one new strain may be efficiently transmitted among humans

2009 H1N1 pandemic (swine flu)

A new virus generated through reassortment of 3 pig viruses, avian and human
viruses (multiple reassortments).
It was unexpected. H5N1was the likely next pandemic but then swine flu came
out.
The virus may have originated in Mexico, and then spread globally in two waves.
There was great concern that this strain may evolve high virulence.
Usually it was a relatively mild strain with most (70%) hospitalizations in people
with underlying conditions.
There was greater mortality in the18-64 ages than seasonal flu. In rare cases it
was unusually severe.
Massive public health response. Was it an over reaction?

This is looking at flue seasons for the past

few years
You get a peak in infections at the same
time every year
The grey line was 2009, swine flu year
and the teeming of it was strange
It didnt fit with seasonal flu. It was a lot
earlier and that is why people freaked out

The H1N1 took over

They did a subtyping to figure out what type of
influenza one has
o Yellow = subtyping not done and orange
= H1N1
Swine flu displaced every other flu that existed
for the next couple of years

This years graph has no orange meaning no H1N1 and that

could be because the flu vaccine has that swine flu variety of
influenza
Successfully reducing H1N1 infections?
Red is H3 and there is a lot of red.
Only 1/3 of sampled H3 viruses have been vaccine strain
That is why people are getting sick this year and saying the
vaccine doesnt work because the vaccine only protects for
1/3 of the H3 virus

Lecture 21: Resistance

The Evolution of Resistance
Malaria: resistance in a parasite and a vector
Antibiotics: resistance in a bacterial pathogen
HIV: resistance in a viral pathogen
Evolution of Resistance in Malaria
50-500 million cases
1 million deaths
Mostly children (480 000) in sub- Saharan Africa died in 2012
o 1300 children everyday
Malaria
Mosquito-borne
Fever and chills
Anemia due to loss of red blood cells
o Parasite gets into blood cell, replicates and then bursts out
Methods of Control
o Drug treatments in humans
o Eradicating the vector (mosquito)
o Decreasing contact between humans and vector
! I.e. using a bed net
Life cycle of Plasmodium
The parasite spends some time in a vector and some time in a human host
Drug Treatment in Humans
There are lots of drugs made to target malaria
One of which is quinine
Drug Resistance in Malaria
Malaria transmission areas
and reported P. falciparum
resistance, 2004
Green part shows where it
is most prevalent
And the dots/triangle and
stars represent where they
found drug resistance to 3
different kinds of malaria
The idea is that for every
drug developed, there has
been resistance evolving
against it
There is a new drug that is super powerful and kills 99% of parasites and they
are now tracking it from South east Asia and they believe were in trouble if it
gets to Africa

Eradicating Mosquitoes I: The larval stage

We can try to control the spread by controlling the vector.
They like to lay their eggs in standing water and small pools
If we get rid of standing water, we can get rid of a lot of mosquitoes quickly
Eradicating Mosquitoes II: The adult stage
Using insecticide on the walls of houses so when they come and land on the
walls, they die
Or spraying whole areas such as fields with insecticide
Evolution of Insecticide Resistance in Mosquitoes
This was done in France on mosquitoes
that transmit viruses such as meningitis
Treatment started in 1968
o They sprayed 20 kilometer radius
from the Mediterranean sea
Treatment ended in 1990
o Were going to look at the
evolution of resistance in the
mosquito population
Insecticide use began in 1968, and was
stopped in 1990
We have x axis = distance from the sea
and y axis = frequency of resistance allele.
The green on the graph was the areas that were sprayed with insecticide and
white was not
Close to the sea there is a high frequency of the resistance allele which
decreases as you get further
o By 1978 the resistance allele was most common near the sea (and
spreading north)
o Why? Because mesquites dont see the 20km boundary and fly over it.
There is no advantage to being resistant in the untreated area. They
mingle with the insects in the treated area so you get lower and lower
frequencies as you more further
o We killed off any mosquito that didnt have the allele
After spraying was stopped, its frequency declined rapidly (suggests a cost)
o It didnt matter where you were, it was about equal frequency
o Were losing the allele and weve stopped selecting on the populations
for resistance
o This suggests that the insecticide WAS the selective force and that there
was a cost to resistance which makes sensitive mosquitoes better in
untreated areas
o Evolution is the change in allele frequencies over time and that is what
the graph is showing

Antibiotics and Bacterial Pathogens

The antibiotic, penicillin discovered in 1929 by Sir Alexander Fleming
Antibiotics kill bacteria by disrupting a variety of biochemical processes
o And then in turn, the bacteria will try to find way around this
They are a major life saver for humans
For bacteria they are a major force of selection
o Susceptible genotypes killed by antibiotic
o Resistant genotypes survive
o Even a little resistance means these bacteria will be in higher frequency in
the population
Therefore antibiotic use amounts to a selection experiment
o Its a selection experiment inside an individual host
Tuberculosis
Common and deadly
Attacks the lungs
Caused by a bacteria
1/3 of all humans have it and it kills up to half
a million people a year
The graph is looking at deaths from
tuberculosis over time
There has been a decline and it has a lot to
do with hygiene and sanitation
Then 2 drugs were introduced and they
really drove the death rate to low levels
The bottom graph looks at cases of TB that
were treated and then the patient got it again.
They looked at these cases and asked what proportion of the bacteria was
susceptible vs. resistant
In the new cases, most of the infection was composed of susceptible bacteria
because it was the first time the patient had it so only 8.2% of the cases
harbored resistant bacteria
In relapsed cases, twice as many patients are harboring resistant bacteria
So the antibiotic treatment is selecting for any resistant bacteria in the host
o You almost clear the infection except the resistant ones get the
advantage and can grow up and harm the patient

Resistance increases with drug use

The red shows the total antibiotic
use in hospitals and it is going up
And you have the rise in
resistance that matches the use of
antibiotic
Antibiotics are the selecting force.
You kill a bunch of things that are
sensitive to drugs, leaving anything
that is resistant to it

Antibiotic Resistance Evolves Rapidly

This graphs shows the
introduction of a drug and
when the first case of
resistance was shown
So normally a drug will be
released and resistance to the
drug is seen a few years later
Something interesting was that
penicillin was discovered in
1943 but the first sign of
resistance was found 3 years
before that
This shows that there is
natural variation in bacteria even before we use an antibiotic
To be sure that it is the drug that is selecting for resistance, we can remove the
drug and see if there is a decrease in resistance
Resistance decreases with decreased drug use
Icelandic health officials campaign to reduce
the use of penicillin
When they first stared to use it, there was an
increase in resistance
Then they lowered the use of penicillin in
Iceland
The result was a decline in the frequency of
resistant strains
This shows that the antibiotics really are the
selective force
The evolution of antibiotic resistance
Use of antibiotics creates a strong selective environment favouring the evolution
of antibiotic resistance

o Sorting resistant from susceptible genotypes (increases the relative fitness

of resistant types)
! Basically, what were doing is killing the susceptible types and
leaving the resistant types to grow up
! This is obviously a problem because although antibiotics are good,
we are just selecting out the resistant types
o Mutation from susceptible to resistant genotypes, facilitated by high
replication rates
! Basically, with short generation time, high replication rate and high
mutation rates, going from susceptible type to resistant is fast
Plasmids and Horizontal (Lateral) Gene Transfer
Bacteria can gain resistance during the same generation and in another way than
through mutation
Resistance genes can be transferred among bacterial cells via extra-chromosomal
loops of DNA called plasmids (bits of DNA)
So if you have a plasmid that confers drug resistance, then you are drug resistant
yourself
Bacteria conjugate and share DNA. When the plasmid is replicating, it can go
into another bacteria
A resistant bacteria transferred a plasmid that confers resistance into a bacteria
that was sensitive
Taking antibiotics kills bacteria that isnt targeted
o i.e. You take antibiotics for your face and it kills bacteria in our gut
o And your gut bacteria now has resistance (Which is good)
o But the risk is if you get an infect that causes you problem, the gut
bacteria can swap the resistance plasmid and make the bad infection
resistant
o Antibiotics do not work against viruses

Horizontal Transfer and Resistance Evolution

Use of antibiotics creates a strong selective environment favouring the evolution
of antibiotic resistance
Use of antibiotics for non- bacterial infections can exacerbate this problem
through horizontal transfer of resistance genes

HIV
HIV is a big problem
But it is most prevalent in Africa
In some African countries, as much as 39% of all adults have HIV
Routes of transmission
Blood transfusion
IDU
Other direct blood contact
Perinatal
Breast milk sexual
In graph A, the beginning of HIV cases started
growing in 1981 and then slowly declined
through drug treatment and precaution but then
it starts to level off because risky behaviour
starts increasing. People think the drugs can
extend life and that HIV wasnt such a big deal
HIV Particle Double stranded RNA virus and it
has reverse transcriptase which allows it to take
its RNA and convert it into DNA That is why it
is a retrovirus. It turns RNA into DNA instead of
the other way around.
HIV Particle
Double stranded RNA virus and it has reverse transcriptase which allows it to
take its RNA and convert it into DNA
That is why it is a retrovirus. It turns RNA into DNA instead of the other way
around
Life Cycle of HIV
HIV attaches itself on to a host (lymphocyte) and inserts itself genome and
enzyme into the host. It then converts the RNA into DNA and then insert that
DNA into the hosts own DNA
Now when the host cell replicates, the virus replicates with it. Then it packages
up what it made and send it out as virions into the blood stream to infect new
white blood cells (lymphocyts). This kills the host cell.
So basically what happens is the persons immune system is destroyed and they
are then susceptible to other infection because their immune system cant do
anything to stop it. They are all killed off
AZT Resistance in HIV
A drug (AZT) was developed in early 1980s
It binds to and inactivates an HIV enzyme (reverse transcriptase) that is required
for viral replication
o So if the enzyme cant do its job, you cant have viral replication
A new mutant enzyme arose with an altered binding site that was resistant to
AZT
The appearance and spread of this mutant enzyme has been documented
repeatedly

Retroviral replication and AZT

The reverse transcriptase uses host
nucleotides and attaches them to the
RNA template
AZT (bottom right), looks just like
thymidine except it has a different sub
group
So if the enzyme picks up AZT and
attaches it, nothing else can bind after
it. It needs an OH to bind.
Viral replication stopped
Then the resistance occurred
HIV populations evolve resistance to AZT within individual patients

The top left graph looks at a patients viral

samples who has been on treatment for months
and asked how much drugs do you need to stop
viral replication
X axis = how big of a dose of the drug are we
using
Y axis = ability to grow in the presence of a drug
If you have a low dose, only about 65% of the
virus is still living and as you increase the drug
dose, you kill more and more
But if you look at the same patient 9 months
later, the dose that was killing most of the virus is now killing only 45%
Then if you look months after, the same dose kills nothing
Therefore the HIV in the host is gaining resistance to the point where the host
needs massive drug does to have any impact at all
This happens in pretty much every patient
The graph in the right shows patients and how long they have been on therapy
and how big a dose do you need to inhibit the viruses by 95%
o If youve been on therapy for a little while, you only need a little bit but if
youve been on therapy for a long time, you need a massive dose

AZT Resistance in HIV

Thought experiment: if you wanted to genetically engineer an HIV virion to be
capable of replicating in the presence of AZT what would you do?
Solution: change the active site on reverse transcriptase, making it less likely to
mistake AZT for Thymidine
o It didnt know before that AZT wasnt a nucleotide. The binding site for
the receptors changed and so the reverse transcriptase was better able
to recognize a real nucleotide from a drug mimic
Why does HIV evolve so fast?
High mutation rate (20-50% errors/replication)

Short generation time (1 year = 300 viral generations)

Massive population size (1010 new virions/day)
Therefore a resistant mutation is generated quickly
As soon as you introduce an antibiotic, you are selecting for resistance and killing
off anything that isnt resistant
One solution is to construct a treatment that requires multiple mutations to
occur
o Make the process harder for the virus
o It is easy to get 1 mutation but harder for 1 virus to get 2 specific
mutations
o One way to do this is with multiple drugs with different targets and
actions

HAART: highly active antiretroviral therapy

HAART is a cocktail of differently acting drugs.
This shows a group of 1800 patients and what happens over
time as you use this HAART
You see a decrease in the number of people dying from HIV
Phylogeny of HIV
They used phylogentic data to try and figure out where
HIV came from
And it came from other primates
There are two kinds of HIV in circulating in humans
o HIV2 doesnt cause as much trouble for its host
o HIV1 causes a lot of trouble and it came from
chimps
HIV1 jumped from a chimp host into a human host 4
times
In order to understand HIV and how to improve
outcomes, we have to look at primates because SIV
isnt virulent in the its chimp host and if we can
understand why that is, we can design better
treatments
How did HIV move from Non-Human Primates to Humans?

It passed on by blood so bush meat is a potential source

Lecture 22: Aging

Aging
Why hasnt evolution gotten rid of aging?
o You could live forever and reproduce forever so why dont we do that?
o Since we dont do this and because there is a lot of variation in this
means natural selection is acting on it
Aging: proximate and ultimate causes
Costs of reproduction
The evolutionary theories of aging
o Mutation accumulation
o Antagonistic pleiotropy
What is Aging or Senescence?
Definition:
o Progressive decline in somatic function reflected in reductions in fertility
as well as survivorship
Proximate cause:
o We are separated into two parts. Soma and the germ line.
o Progressive degeneration of the soma
o the decline in bodily functions over time
Manifestations of Aging
General degeneration of the soma
o Impaired function (speed, strength,
sight, etc)
! Lower rate of reproduction
o Increased disease (cancer, organ
failure)
Mortality rate increases with age
o The probability of a 5 year old dying
before the age of 6 is pretty low
o But the same probability of death
between 96 and 96 is quite high (graph)
Senescence: An Evolutionary Mystery
Observation:
o We have evolved to age and die
Explanation?
o Appears to be non-adaptive in the extreme
o How has evolution favoured aging? It serves no benefit. Wed be better
off if we could reproduce and not die off.
Aging at Different Rates
Humans and Fulmars
o A Scottish ornithologist studied the fulmar birds. There was a picture of
the bird and him when he was 22. The bird was tagged as bird number 64

o He goes back when he was 64 and the bird doesnt look like it aged at all
based on how well it in functioning
o The fulmars age at a slower rate than people
o There is large variation in aging rates between species
Bristlecone Pine - 5,000 years
o Can reproduce the entire time
May fly 1 day
o They are born in water and live in it for 1-2 years. Then they fly off and
mate. The females lay their eggs in the water and then die instantly
o Their adult lifespan is one day

Medical Views of Aging: Headlines

Eat your ACEs:
Vitamin E extends lifespan
(vitamines)
Exercise:
Run to reduce heart disease
Diet restriction:
Eat less, live longer
Get rich:
The rich live longer
But WHY has aging evolved?
Free Radicals and Vitamins
One cause of aging is damage to cells through free radical production
Molecules containing at least one unpaired electron and can damage parts of the
body
Attack and modify macromolecules
o Oxidation of DNA, proteins, lipids
We have our own defenses (various amino acids that act as antioxidants)
Vitamins E and C can act as antioxidants
We also have repair mechanisms
***Why not enough repair?***
o Why arent these repair mechanisms better? There has to be constraints.
Life Without Constraints
Imagine an organism with no constraints. This is called a Darwinian demon
Darwinian Demon?
o The ideal organism would maximize all fitness components simultaneously
! Begin reproducing at birth
! Reproduce at an infinite rate
! live forever
! This is hypothetical. No organism actually does this
o But
! Biological systems are constrained
! Constraints often take the form of trade-offs
Trade-offs Affect the Evolution of All Traits
Display size (morphological trait)
o Peacock story. Tail is good for mate and bad for longevity
Foraging rate (behavioural trait)

o More time you spend looking for food, the less time you spend looking
for predators
Longevity (life history trait)
Even though resources do not limit humans, they are limited by the constraints
of the body i.e The metabolism and other features

Free Radicals and Vitamins

Molecules containing at least one unpaired electron
Attack and modify macromolecules
o Oxidation of DNA, proteins, lipids
We have our own defenses (various amino acids that act as antioxidants)
Vitamins E and C can act as antioxidants
We also have repair mechanisms
***Why not enough repair?***
o DNA repair mechanisms are energetically costly so if you invest more in
it, there will be less energy for reproduction
o So, you would have to increase longevity at the cost of fecundity
Trade-offs may govern the evolution of DNA repair mechanisms?
We dont live longer because of the trade off explained above. We would
sacrifice fecundity if we tired to live longer
Costs of Reproduction
High reproductive rates accelerate senescence and thereby shortens life span
o Reproduction is costly and will shorten lifespan
o Why dont we reproduce more? Because it is costly to longevity so those
2 things will balance out at some point
Reproductive Costs in Waterstriders
We can find out if there are costs to high reproduction by manipulating the
reproduction rate
o The individual is spending more time and resources on reproduction, so
there should be less for longevity
o So if we force individuals to reproduce more, it should impact their
longevity
Female waterstriders skim along water looking for insects and when they find
one, they suck out the guts and convert the protein into eggs. So females are
limited by food. The more they can catch and eat, he more eggs they can make
Prediction:
o Females induced to reproduce at a high rate will have reduced longevity
Test: Female Waterstriders
Hypothesis:
o High reproductive rates accelerate senescence and thereby shorten life
span
Design:
o Manipulated reproductive rate of females by changing food ration

Data:
o

Reproductive rate and longevity

Longevity

They measured reproductive rate and how many eggs they made to verify that
this food manipulation was viable for change in reproductive rate and then they
measured how long they were living
They also measured the quality of the eggs
o Senescence is the deterioration of
the soma so as they are
deteriorating, they might make
worse eggs because the eggs are a
product of the soma
Graph shows reproductive rate and
longevity and it looks exactly as we
predicted
o Those who have a lower
reproductive rate have a longer
life span and females that
reproduce as a high rate have a
low life span
o Reproduction is a huge cost
Senescence of the mother can be seen in
age-related declines in the quality of her
eggs.
Top right = normal development
Bottom left: The process of development
can stop along the line of development or
it can stop when the babies are trying to
emerge from the eggs and they cant so
they die
Bottom right: they arent developing
properly and it leads to nothing
So if we lowered longevity by increasing their reproductive rate, we should see
more of the bad eggs
And that is what they saw

Reproductive senescence occurs long before mortality

Deterioration happens before death

This graph shows what the survival curve
looks like.
They slowly start dying off and then they
are all dead by 90 days

This was done by Penolope Gordon and she also measured when reproduction
stopped
o They stopped producing eggs long before there was a high risk of dying
o This is like menopause in water striders
o Before reproduction stops, they produce eggs that arent developing
properly

Costs of Reproduction
Taxa
Methods
Crustaceans
Diet restriction
Insects
Egg addition
Fish
Removal of oviposition sites
Birds
Delayed reproduction
Mammals
You can take eggs from one birds nest and put it in another birds nest so the
cost of reproduction isnt in producing eggs but in provision for young because
youre forcing the bird to invest more in reproduction and thus deteriorate
faster
The birds you took eggs from can live longer and make more eggs
Conclusion
There is a cost of reproduction
Increased rate of reproduction comes at a cost of reduced longevity
Implication
o Trade-offs are involved in the evolution of senescence
! We cant live forever because we also need to reproduce
Humans?
o Its hard to do in humans but you can still find data
A Study of Reproductive Costs in British Aristocracy
Genealogical records of 1200 years (740-1875)
o Lords and ladies and basically royal people kept records of themselves
o We can look at the number of babies a person had and how long they
lived
19,830 males
13,667 females
Studies of humans rely on correlation rather than experiment
So those who reproduce at a high rate will have lower life spans
This is not an experiment. Just correlations so there might be a correlation
between low longevity and high reproduction rates but it might not have
anything to do with trade offs
Mortality Among British Aristocrats (female)
The basic expectation is that if there is aging, the
probability of death per year should increase

We see exactly what we expect, mortality increases with age for the mothers
born before 1700 and have 2.8 offspring on average
o There was a lot of childhood mortality so that is the reason for the dip in
the curve
For mothers born after 1700, the curve is lower and these mothers have fewer
offspring
This fits with our prediction
o These mothers invest less in reproduction so they can invest more in
longevity
o But this is a correlative study
o A lot of difference before and after 1700
o The women might have less babies but they probably have better access
to health care and they might have better hygiene
o There are a lot of reasons why mortality rate drops for this group which
has nothing to do with reproduction
o So we can look at each individuals mother and compare it to other
mother and see how many babies they had versus how long they lived

Costs of Reproduction in British Aristocrats

This graph shows number of kids as a function of age at
death
Overall, if you have more babies, you dont live as long

Sex Differences in Aging

In mammals, females typically outlive males
This is believed to be related to the costs of male competition (aggression, risk
taking)
In most human societies, females outlive males
o But there is variation in by how much they out live males
Can we detect some role of reproductive costs given these variations
Sex Differences in Aging & Costs of Reproduction
The dots are showing different populations around the world
X axis = how many babies did they have
Y axis = the difference in the life span of males and females
High birth rates reduce the relative survival advantage of females
females live way longer than males (14 years more than males) when the
birthrate is closer to zero
And the down where females are having lots of kids,
females are living slightly longer
When females dont make babies, they live longer than
males
When females invest more in reproduction, that number
goes down and they live about the same
This shows that there is a cost to reproduction

Madame Jeanne Calment, Died at age 122, 1997

Had one child
Her age was unambiguous
Other people have tried to say they lived long but there was no proof
Theories of Senescence
Mutation Accumulation: peter Medawar

Deleterious mutations with agespecific effects accumulate at late

ages
If mutations have deleterious
effects and those effects happen
later in life, selection will have a
hard time weeding those mutations
out.
If the effect doesnt show up until
after you reproduced, selection
cant weed it out

Antagonistic Pleiotropy: George Williams

Genes with beneficial effects early
in life will be favoured in spite of
negative effects late in life
These genes have a benefit but if
the detrimental side doesnt show
up until after reproduction then
selection cant weed it out

Both rely on the fact that the strength of selection declines with age
Natural selection, which relies on differences in the reproductive success
between individuals, ignores how an individual functions late in life. - Ackermann
& Pletcher 2008 in Evolution in Health & Disease, 2nd Ed.

Age Profiles
If there was no aging and no other
forms of death, you would live
forever but infection and accidents
happen so even if we didnt age,
something would kill us
So in out hypothetical world where
we dont age, we have a 10%
probability increase for death du to
external reasons
o 10% externally imposed mortality per year
Predation, accidents, parasites
Few live to very old age
You cant live forever because ever year, there is an added 10% chance of dying
Most people in this graph arent living to the age of 14
Since most people dont make it to this age, what happens at this age and beyond
doesnt matter to evolution
Mutation Accumulation Theory
Few survive to older age, and those that do have already reproduced
Strength of selection declines with age because so few individuals survive to that
age

Late acting deleterious mutations are not under strong selection and, thereby,
accumulate.
Old age is a dust bin of late acting deleterious mutation

Mutation Accumulation
Imagine we have 2 genes that have
the same deleterious effect
(reduce survivability by another
10%)
One of the genes acts early in life
while the other acts late in life
One increases you chance to die
by 10% at age 3 while the other
does so at age 13.
They have the same potential
So individuals who make it age 3
and die will be weeded out
because thy probably havent reproduced. They died and didnt pass on their
genes
But for the other gene, very few people live to actually see the effect
If a bunch of them have this gene, tons of them die due to normal mortality and
very few make it to age 13 so the average effect of the gene is small because for
some individuals the effect was 0. They already had reproduced and died for
other reasons
For the age 3, gene, the realized effect is high because most people make it to
that age but for age 13, it is low because very few people make it to that age
Evidence? (Single Gene Effects)
Severe diseases that act early in life (pre-reproductive) are rare: 7%
o One example of such is Tay-Sachs disease but it is rare
Most such diseases act during or after reproduction: 93%
o An example of this is Huntingtons disease. It is a dominant single gene
that shows its effect later in life.
o A famous singer found out he had the disease when he was 40 but by
then he already had 3 kids and there was 50% chance he passed it on to
each of them
o If the effects had shown when he was 15, he wouldnt have had those kids
and selection would have weeded the gene out
Antagonistic Pleiotropy
Pleiotropy = gene that has multiple effects. It will
affect 2 different fitness components. Antagonistic
mans that it will affect them in different ways. So it
might be good for one component but bad for the
other
Few survive to old age, and those that do have
already reproduced

Strength of selection declines with age

Genes with beneficial effects early in life will be favoured in spite of negative
effects late in life
Since selection declines with age, selection cares less about the negative effects
because the impact is so small
The benefits are great early in life and most people are alive to see it but most
people are not alive to see the negative effect
So if there is a benefit, selection will go for it even if there is a negative effect
later in life because most people wont be alive to realize the effect
This gene would spread a lot because of the benefit in early age
This is analogous to reproductive allocation
You might increase early life fecundity for the cost of reducing longevity
(negative effect late in life)
So reproductive cost is analogous to Antagonistic Pleiotropy

Experimental Evolution of Aging

Can we evolve things to live longer?
Fruit fly
Michael Rose
Looked at 4 different types of females
Costs of reproduction in flies
A. Normal
a. Have a 40 day life span but if
you change their reproductive
allocation so they invest less in
reproduction (by the means
below), you extend their life
span
B. No Ovaries
C. Virgin Females
a. Makes them make fewer eggs
D. Sterile Females
Experimental Selection Lines:
Tried to select for early or late fruit flies
Put agar in a test tube with food, put in the flies, let them mate and lay eggs, then
dump out the flies and leave the eggs and you have the next generation of flies
Do this over and over and this is a selection experiment
Natural Reproduction (N)
o Eggs from young (day 14) females used to start next generation
o Life past day 14 is superfluous
! Since they are being dumped out after day 14, it doesnt matter
what they do after. All that matters is how many eggs they lay
Old-age Reproduction (O)
o Eggs from old (day 28) females used to start next generation
o Females had to survive to an old age to contribute to the next generation

o Old females that produce the most eggs will contribute the most to the
next generation
o He took eggs from day 28, earlier eggs did not matter
o By taking eggs from females that survived to day 28, you select strongly
for females to live that long
o These females show evolved to live longer because the day 28 females
are the only ones contributing to the next generation
o They should also have greater fecundity because we only selection the
ones that make lots of eggs later in life
o And if Antagonistic Pleiotropy is playing a role, wed expect early life
fecundity to be reduced
Roses Experiment

Eggs from the natural reproduction

live for about 37 days
The flies that had old age being
selected for lived for about 45 days
and that is like 20 extra years in
human life
So yes, you can evolve things to live
longer

Predictons
O lines will evolve greater longevity
O lines will evolve greater late life
fecundity
If antagonistic pleiotropy is playing a
role
o O lines will evolve reduced
early life fecundity

Predictions: Antagonistic Pleiotropy

This graph will show the flies that
went through the old selection
experiment vs. the natural
reproduction selection experiment
and what their fecundity is for
different ages
If there is no effect, then the number
of eggs by females from both
experiments should be the same.

o The natural female should lay the same number as the old experiment
female
Were expecting the old ones to lay eggs at later ages but if there is Antagonistic
Pleiotropy, well see reduction in early life

Results II: Fecundity

This is what the data looked like, it was

exactly what you predicted
The old one have higher reproduction at
late ages but it came at the cost of
decreasing reproduction at earlier ages

Conclusions:
Rate of senescence can evolve
o The flies evolved to age more slowly
Antagonistic pleiotropy appears to be playing a role in why we age
Selection in early life fecundity is deceasing late life fitness
Theories of Senescence
Mutation Accumulation
Deleterious mutations with age-specific
effects accumulate at late ages

Antagonistic Pleiotropy

Genes with beneficial effects early in life

will be favoured in spite of negative effects
late in life
Both rely on the fact that the strength of selection declines with age

Lecture 23: Final topics in Evolutionary Medicine

Evolution in a vaccinated world

Environmental change and health
o Myopia
Medical Physiology
o Fever
Menopause

Vaccines
Vaccines are biological treatments meant to improve immune responses to
future exposures to specific diseases.
In essence the antigen in the vaccine primes the immune system so that it may
respond quickly to future assaults.
o It stimulates an immune response so it youre exposed to that pathogen,
your immune system can combat it
Vaccines are often dead or living (but attenuated) pathogens.
Alternatively, they are parts of the pathogen, or its toxic agent, that elicit a
response by the immune system
Common vaccine types
Live Attenuated
o Live but less harmful version of the pathogen
o polio (OPV), measles, mumps, tuberculosis
Killed
o polio (IPV), flu (injected), cholera, hepatitis A
Toxoids (inactivated toxic compounds)
o Part of a pathogen
! The immune response targets the
o Diphtheria, tetanus
Smallpox
Smallpox is a virus that was once widespread and led to sometimes fatal
infectious disease
Spread by inhalation of airborne virus particles or direct contact or contact with
contaminated material
A world wide vaccination program eliminated the disease
Last case in Canada 1946, and in world 1977 (Somalia).
o We successfully got rid of small pox with vaccination
The smallpox vaccine
In the 1700s it was common knowledge that milkmaids did not get smallpox.
Milkmaids did get a much less virulent, though similar disease, cowpox.
In 1796 Jenner began exposing patients to the puss from blisters of infected
milkmaids.
He subsequently determined those patients were immune to smallpox.

o He took a related pathogen (the cowpox pathogen) and used it on

people and it was similar enough to small pox that it primed the peoples
immune system against small pox
People in china and India were doing this thousands of years before

Vaccine preventable diseases

Anthrax
(Swine Flu)
Cervical Cancer
Influenza
Diphtheria
(Seasonal Flu)
Hepatitis A
Japanese
Hepatitis B
Encephali's (JE)
Haemophilus
Lyme Disease
influenzae b
Measles
Human
Meningococcal
Papillomavirus
Monkeypox
(HPV)
Mumps
H1N1 Flu
Pertussis

(Whooping
Cough)
Pneumococcal
Poliomyeli's
(Polio)
Rabies
Rotavirus
Rubella
(German
Measles)
Shingles (Herpes

Zoster)
Smallpox
Tetanus
(Lockjaw)
Tuberculosis
Typhoid Fever
Varicella
(Chickenpox)
Yellow Fever

Evolution in a vaccinated world

Pathogens evolve in response to our attempts to get rid of them
Antibiotics are failing with increasing frequency, due to evolutionary responses.
What about vaccines?
Immune systems are sources of massive selection on pathogens (e.g., flu).
By activating an immune response, vaccination can be viewed as a potential
sources of selection on pathogens.
o If you stimulate pathogen activity, it can drive pathogen immunity.
Vaccines stimulate pathogens and thus will be selecting on pathogens
Given widespread vaccination, should we be worried about its evolutionary
effects?
3 risky assumptions (3 reasons why we shouldnt be worried):
o Vaccine-induced immunity simply replaces natural immunity, therefore no
evolutionary consequences are expected.
! People gain immunity naturally so this shouldnt change anything
o Vaccination has worked effectively for 100+ years. Any consequent
problems should be obvious by now.
o Even if vaccine-resistant mutant pathogens do evolve, they will do less
harm than wild type pathogens.
Three case studies that disprove the 3 arguments
Hepatitis B
Diptheria
Malaria
Hepatitis B virus
There are 6 different strains of it and
they share a common amino dominant
region (a determinant that is outside)

The vaccines is targeting the antigen on the surface of the virus

Globally significant cause of hepatitis, liver cirrhosis, and liver cancer.
Current vaccine is effective.
Vaccine targets the a determinant (a major
surface antigen)
A vaccine resistant type mutant occurs at low
frequency in vaccinated individuals.
o The mutation was on that area and it
was a single nucleotide change (G to
an A). This resulted in an argenine
instead of glycine
Mutant allele is increasing in frequency in
vaccinated people
Thus the HBV populations are evolving in
response to vaccine
The mutant virus has an advantage, it can
survive and escape immunity and then spread through the population
Looks like vaccines are driving evolution and selecting for the mutant type.

Malaria

Disease caused by protozoan, Plasmodium.

No current vaccine in use, though trials are occurring.
o The problem is that the vaccine targets tend to be polymorphic
Plasmodium is polymorphic for genes underlying their antigens.
Trials using vaccines with a subset of these antigens demonstrated that nonvaccine alleles rapidly increased in frequency.
In this CSP gene, it is the target of
a vaccine called RTSS, there are
two little areas that the vaccine is
targeting TH2 and TH3.
RTSS was made by using a lab
strain of malaria to concoct
vaccine. Thus making it
monolavent. It protects against
just this one strain but they
believe that it will confer
immunity to closely related strains and if there isnt a lot of variation in the CSP
gene, then were golden
They did a test by looking at the CSP gene in malaria parasites from people in
Malawi. In a lot of the regions there was no variation in the CSP gene but there
showed variation in TH2 and TH3 which was exactly what RTSS targeted
So malaria has a pile of variation in the thing that the vaccine is trying to target
So you might have immunity to some of them but it wont be all of them
It was a small sample but they found 57 types of CSP genes
The frequency of alleles that are not contained in the vaccine strain does
increase in the population when you start vaccination

Diptheria

Upper respiratory disease caused by bacterium

Toxin producing strains cause lesions on tonsils,
nose, larynx, and pharynx
Vaccines consists of detoxified toxin (toxoid). And
has been highly successful in reducing childhood
mortality
In places where they did vaccinations, the frequency
of Diptheria strains that produce toxins is going
down and this might be because it is costly to make
he toxin. If youre a Diptheria virus and youre in someone who is vaccinated,
you could be sending toxins out into the host but the host is neutralizing it. It
proves to be costly so the frequency goes down
Some of this may be attributable to reduction in the frequency of the toxin
producing strains

Can vaccines alter the course of evolution of their targets?

Yes!
Evolution occurs through:
Sorting of existing strains, favouring the non-vaccine strain (Pertussis,
Pneumococcal disease, Diphtheria, Malaria)
o Any strains not in the vaccine will increase infrequency (same has drug
resistence).
Mutation to new non-vaccine strains (flu, hepatitis b).
The evolutionary responses might not always be bad (Diptheria)
o The frequency of toxins went down
Why has vaccination worked so well despite evolution?
Vaccination has successfully eradicated smallpox
Close to eradicating polio
Provides widespread control of measles, pertussis, diphtheria, mumps and
rubella.
It is because not all infectious diseases are alike
o Vaccine success stories tend to involve acute childhood infections
o We have success when we target childhood diseases
Natural history of vaccine success stories
Acute infections either kill the host or are rapidly cleared.
Infection invokes immunity that is broad and life-long.
o Your immune system can target a lot of strains similar to what you were
infected with
o I.e. If you had measles and survived, you have life long immunity to it and
other strains of it
These pathogens persist by exploiting susceptible individuals, which are typically
children.
o Children are new to the population and have not developed the immunity
so they are more susceptible

It is not clear why the pathogen has not broken through the immune response.
o The pathogens have not figured out how to get around this immunity but
if they could, they would have a huge pool of people to infect but they
cant.
Thus, the immune response seems evolution proof, and all vaccines needed to
do was to induce it.

Target diseases of vaccine development today are much different from those of vaccine
success stories
The diseases were trying to treat with vaccines are not those types of diseases
Pathogen populations tend to be polymorphic. Many different strains mean many
targets for vaccine.
Some strains can infect hosts that have immunity to other strains (flu, malaria).
o You can have immunity to one strain but another strain might be
different so you can still be attacked
Individual infections are often chronic (malaria, HIV, tuberculosis), persisting in
partially immune hosts, due to immunosuppression, and antigenic variation and
evolution.
o Certain diseases can generate chronic infections that are long lived and
they are long lived because:
! You just cant clear it because it keeps changing (mutating) and
the immune system cant keep up with it
! So HIV and malaria and other diseases like this have figured out
ways around our immune systems
! So generating an immune response against this wont work as well
as it did with measles, mumps, Rubella etc because they figured
out how to get around it
Evolution in a vaccinated world
Vaccination has been one of the great advances of human health
However, vaccines can cause evolution of the pathogen
This can have positive or negative effects
Research focuses on how best to manage this fact.
It is early in the game.
Evolutionary Comparative Studies And Human Disease
One of the reasons were mismatched with disease is because of mismatch with
modern environments
o Humans have been evolving for about 200 000 years
o Weve had agriculture for 12 000 years
o And weve had antibiotics for 100 years
o Our environment is changing incredibly rapidly and evolution might not
be able to keep up
o And because most of our evolutionary environment was in a different
environment, it may explain some of the health problem we have now
Comparative studies may point to an answer in evolutionary history for threats
to health today.

Basic approach is to compare so-called primitive societies and their life styles
to modern societies.
o Compare societies what live a closer life to what we had in the past with
the modern ones
o These people who live in
Mismatches may account for some diseases.
We may be adapted to a different environment and life style than the one in
which we live.
Were using myopia and an example

Myopia
Myopia is near sightedness. Distant objects are out of focus. Caused by and
elongated eye
Varies in frequency among nations
o China, 50-70%, Sweden 30%
o Low in indigenous peoples
Has increased over time
The graph on the right shows that the frequency
of nearsightedness is rising is these 4 countries
There are several estimates of high heritabilites
of myopia and to test this, they looked at twins.
o Monozygotic twins share all their genes
and dizygotic twins share half their genes
o Then they asked, of these sets of twins, if
one is nearsighted, is other near sighted
as well (concordant pair) or does one have nearsightedness and the other
does not (discordant pair)?
o What they see is that more often, the monozygotic twins are concordant
pairs and the dizygotic twins are discordant
o This means that nearsightedness is heritable

o
Why has evolution led to a trait that would surely have reduced fitness in our
hunter-gatherer history?
o If you were a hunter and you couldnt see a predator from far away, it
would be bad for you. Why hasnt evolution weeded this out?
There are environmental correlates.
o Schooling
! If youre reading a lot of books in artificial light, your chances of
getting nearsightedness is higher
o Lack of exposure to sunlight
There is evidence that developmental environment effects the shape of the eye.

Myopia and a GxE Interaction

Remember reaction norms and how genes have different phenotypes depending
on what environment they are expressed in
One possibility is that these same
genes did not cause myopia in our
past environments.
e.g., modern lifestyle includes much
reading under artificial light, during
development.
So maybe the effects of these genes
are different in the past environment
vs. the modern times
You have one genotype (Green),
which is the non-myopic genotype.
While looking at this gene, there is no myopia in the past or the present so this
gene does not code for myopia
Then we have this other genotype (red) that causes nearsightedness. The idea is
that in the current environment, there is a rise in nearsightedness
o But that this is a plastic trait and in the past where there wasnt much
reading or artificial light, it wouldnt have led to myopia
e.g., modern lifestyle includes less time spent outdoors.
o In the past they spent more time in the sunlight so something about real
light means that they didnt develop myopia even with the given genes
o But in current time, where we spend much less time outdoor, those
genes will express themselves so you have nearsightedness
There was a paper that showed that sunlight might protect you from myopia
o Children need 3 hours at 10 000 Lux (unit of sun measurement) a day
! This is about the same as someone sitting under a shady tree,
wearing sunglasses on a bright summer day
! A classroom is no more then 500 Lux
o They did a study in Taiwan where a school sent the kids out for an 80min
break instead of letting them choose to stay inside and after a year, only
8% had myopia where another school that didnt do this saw 18% myopia
! Assuming the frequency underlying myopia doesnt vary between
the schools, so it is an environmental effect
Myopia
To test this researchers studied a population that had only recently adopted a
modern lifestyle (Inuit in Barrow Alaska).
The prediction was that myopia would be more frequent in younger age groups
because they developed in modern environment, including much reading.
Same genes but the effects are different because they grew up in different
environments
So from the study, the predictions fit.
o You have a small
population of related
individuals but the

Fever

younger generation has a much higher proportion of nearsightedness

o The argument is that these are the same genes except in the past these
genes arent expressed because the environment was different
Sometime what we think is disease is actually defense for disease
Fever, elevated body temperature is a common response to pathogen infection.
A common response is to take aspirin, acetaminophen, or ibuprofen.
Is this a good idea?
Why do we run a fever?
o The answer to this question will tell us if treating a fever is a good idea

An evolutionary perspective on why we run a fever

Two hypotheses:
o Fever results from a manipulation of the host by the pathogen.
! Maybe the pathogen likes a warmer host
! Prediction: fever increases the pathogens reproductive rate. A
fever is goof for the pathogen
o Fever is an adaptive defense against the pathogen.
! The pathogen would reproduce at a lower rate and transmit at a
lower rate
! Prediction: fever decreases the pathogens reproductive rate.
To test this, they did an experiment on desert iguanas
Behavioural thermal regulation in an iguana
Iguanas are ectotherms (they cant regulate their own body temperature), and
therefore behaviourally regulate their body temperatures.
o So if they want to warm up, they have to go bask in the sun
Iguanas injected with live bacteria tend to bask and elevate their body
temperatures.
o By injecting the bacteria, they would go into the sun and warm up in the
sun on purpose
You dont even have to inject a live pathogen. You can inject a dead one and
they will still do this behaviour
o This means that the pathogen isnt doing it. The iguana is changing the
behaviour
Adaptive value of fever
Infected lizards were held at a series of
temperatures, and prevented from behaviourally
regulating their temperatures.
o Forced them to stay in different
temperatures
The graph shows the survival rate of the iguanas
after they go the infection and were forced to
stay in different temperatures
Lizards held at fever level temperatures tended to live longer.

It seems like fever is a useful defense for iguanas so it would be bad to control
the fever of an iguana because it is increasing the iguanas survival
Dont provide aspirin to lizards!

Fever in humans?
Cant (easily) experimentally regulate body temperature in
humans.
o Approach: experimentally induce a cold.
Test for effectiveness of treatment in reducing symptoms (effect
on immune response).
We are looking at symptoms of a cold (How stuff their nose is)
when people are given no treatment or they are given one of 3
treatments that is targeted at reducing fever
We are targeting a symptom, not the actual virus
The people with the placebo had no change but the people who
took the medication had their symptoms worsen
Symptoms worse in those taking medicine aimed at reducing fever.
Immune response is suppressed in individuals given anti-fever drugs
Here they looked at how good
the immune response is over the
course of a cold
If you are given a placebo, and
your fever is not being treated,
you develop immunity over the
course of the infection and that
immunity is targeting the virus
If youre given an anti-fever
treatment, the immunity develops
more slowly into a lower level
So the anti-fever treats are
reducing the immune response against the virus itself
So if someone asks, it is best to talk to a real doctor. They will usually say that
when you have a mild fever taking the drugs isnt beneficial but if you have a high
fever, it is beneficial because high fever can do a lot of damage
Menopause
Marks the cessation of ovulatory cycles, reproduction ceases
Affects all women at about 50 yrs
o At this age, they stop being able to reproduce and stop releasing eggs
every month
Most, but not all, other mammals appear to reproduce until death in the wild
o Youd think that if you keep living, you should keep producing babies
because it increases fitness
o If you can produce babies, why would you stop?
o This is the increasing evolutionary question for menopause

Menopause: Hypotheses
Blessings of modern life
o Menopause occurs as a cultural artifact of extended lifespan
! Our environment has changed so much in a short period of time
and maybe weve extended the life span so much that were
experiencing the effects of not being able to have babies at later
ages
! The point is back to when we didnt live this long, any damage to
the reproductive system after a certain age wouldnt have been
visible to selection
Think about the late life deleterious mutation that
selection cant weed out from the aging lecture
You can think of menopause as a late life acting deleterious
mutation that selection hasnt seen before
o Women now do live considerably longer, but this is largely the result of
reduced juvenile mortality
! But even in the past, if one could live past being a child, you could
live to 50 or 60
o Menopause occurs in traditional hunter/ gatherer societies
! So it isnt just the mismatch of the environment that we discussed
with myopia
o Although not common, menopause does occur in many wild populations
(e.g. chimpanzees, elephants, lions, whales)
Good mother
o Females stop reproduc1ng so that they may full care for current offspring
(and grand-offspring)
! I can keep reproducing but Id have so many babies that I wouldnt
be able to provision very well so they would be bad babies at
lower qualities
! So if I stop reproducing and take care of the babies I already have,
that might be better
o Some support
! in all species where menopause does occur in wild populations
(e.g. chimpanzees, elephants, lions, whales, humans), offspring
appear to require extensive maternal care
The idea is that if you have an offspring that needs a lot of
care, if you ignore that baby and have another offspring,
then you have two babies that need a lot of care and you
wont be able to provision both of them properly
So if you stop reproducing and take care of the baby that
already exists, it might be better for your fitness
Menopause in Killer Whales
Mother whales go through menopause at 30 or 40 but they can live up to 80
years in the wild
o So what is the fitness advantage of the long period of not reproducing for
whales?

Contrast the survival of offspring when mother is alive or dead, where alive
mimics presence of menopausal mother.
Expect the presence of mothers, even older aged mothers to increase fitness of
offsprings
Males mate outside the group, females mate inside the group.
o Whales hang out in maternal groups but then leave and hangout with
other groups
Males offspring do not compete for resources with the family, therefore more
care should be directed toward sons.
o So the thinking is that since the
males dont compete for
resources in the maternal groups,
it might be better to divert
resources into that male so it can
be a better competitor in another
group
o Males might require more care
The Contribution of Post-menopausal
Mothers
o Red = female offspring survival
over time. As they get older,
fewer of them are surviving
o The little divergence shows that if
a female loses her mother at the
age of 35 ( a middle aged whale),
her survival drops so having her
mother around is important for
her survival
o The effects on males are even more dramatic, if they lose their mother at
35, their survival drops but if they lose her at 15, it drops even more
o This shows that the offspring have an advantage if the mother stays
around so having an old mother that isnt making more babies is useful
for the whales

Menopause in Humans
Use exactly the same approach, but used church records as data sets.
Pre-industrial farming families in the 18th and 19th centuries
Finland: 537 women born between 1702 and 1823
Canada: 3,290 women born between 1850 and 1879
And we ask the question, is there a benefit to having a grandmother around
One hypotheses is that you might want to stay around to improve the fitness of
your offspring as well as your grand offspring

Menopause in Humans
Offspring with living grandmothers:
o Breed earlier
o More frequently
o More successfully
Top is the Finnish data
The bottom graph is the data from
Canada
And what the graphs show is that if
grandmother live longer, more
grandchildren are born
X axis = age of grandmother and y
axis = how many grandchildren are
born
Obviously the grandmother isnt
contributing to the babies being born
but maybe she is contributing in
helping raise the babies so the mother
can then have more children
So even though she stopped
reproducing, she gets the benefit of having her genes passed on to her grand
children and she can have an effect on how many grand children she has by
staying alive.
Take home messages
Pathogens evolve in response to our control methods (vaccines included).
Mismatch between modern environments and the environment in which humans
largely evolved may explain the prevalence of certain diseases.
Some symptoms of disease are actually our defenses.
o These are some of the reasons why were still vulnerable to disease.
(From the first lecture on evolutionary medicine)
Why human females have a prolonged period of post- reproductive life is a
puzzle. Possibly one solved by looking at benefits of forgoing further
reproduction to focus on current offspring fitness.