Variation!-!

I"

Dr. Gayle Ferguson"

Previously"

Origin of genetic variation - mutations,

recombination"
These processes bring about the variation
on which selection can act, resulting in
evolution"

Understanding genetic variation"

Genetic variation is the foundation of evolution"
"
Understanding the processes of evolution requires knowledge of
variation and how it is transmuted into evolutionary change"

Variation"

Genotypic"

Environmental"

GxE"

Variation can be due to our inheritance

but also due to environmental conditions
like climate and diet"

Understanding genetic variation"

Environment directly affects phenotype and may be
independent of genetics"
"
> Sex determination in reptiles and fish"
> Wing development in insects"
> Congenital differences"
"

Variation in
aphids due to
environment!

- early in year"
- no wings"

- late in year"
- wings"

BUT:"
Evolution depends on genetic variation"

Important to determine whether variation is genetic,

environmental, or a combination of both

Distinguishing between sources! of

variation"
Phenotypes can be experimentally crossed to F1 and F2 and
backcross progeny."
Making use of Mendelian ratios as controls."
Correlation of phenotypic characteristics amongst and
outside of kin."
This however needs to be controlled for similar
environmental backgrounds of kin"
Common garden experiments in which offspring of
phenotypically distinct parents are reared in a
common environment."

Environmental"

Predisposition for being tall is not enough if diet is not adequate."

Bonsai trees are genetically the

same as their larger
counterparts"

Epigenetic!variation"
EPIGENETIC MECHANISMS

HEALTH ENDPOINTS

are affected by these factors and processes:

t Development (in utero, childhood)
t Environmental chemicals
t Drugs/Pharmaceuticals

t
t
t
t

t Aging
t Diet

Cancer
Autoimmune disease
Mental disorders
Diabetes
EPIGENETIC
FACTOR

CHROMATIN
METHYL GROUP

CHROMOSOME

DNA
DNA methylation
Methyl group (an epigenetic factor found
in some dietary sources) can tag DNA
and activate or repress genes.

GENE

HISTONE TAIL
HISTONE TAIL

DNA accessible, gene active

Histones are proteins around which

DNA can wind for compaction and
gene regulation.

HISTONE
DNA inaccessible, gene inactive

Histone modification
The binding of epigenetic factors to histone tails
alters the extent to which DNA is wrapped around
histones and the availability of genes in the DNA to
be activated.

Getting back to basics"

In the most simplistic case a trait is controlled by a single gene
The gene can have two alleles, say A and a!
Hence the possible genotypes are:"
AA

Aa

aa

Homozygous Heterozygous" Homozygous

for A!
for a!

Genotype frequencies in
the population:"

H"
So"

D+H+R!=!1"

R"

AA

Aa

aa

H"

R"

What are the allele frequencies in the population?"

"
Two alleles: A and a!
!
The frequency of A is represented as p!
!
The frequency of a is represented as q!
"
"

p + q = 1"

AA

Aa

aa

H"

R"

What is the frequency of the A allele ?"

AA

Aa

aa

H"

R"

What is the frequency of the A allele ?"

p!=!D+H/2"

AA

Aa

aa

H"

R"

What is the frequency of the A allele ?"

p!=!D+H/2"
"
similarly!
!

q = R+H/2"

AA

Aa

aa

H"

R"

What is the frequency of the A allele ?"

p!=!D+H/2"
"
similarly!
!

q = R+H/2"

But
So"

p+q!=1
q!=1-p!

we need to track only p!

AA

Aa

aa

H"

R"

What is the frequency of the A allele ?"

p!=!D+H/2"
"
similarly!
!

q = R+H/2"
Note that from the genotype frequencies one can
always calculate the allele frequencies!
However,"
the opposite is not true!!!"

But
So"

p+q!=1
q!=1-p!

we need to track only p!

A simple population genetics model"

AA

!Aa"

aa"

A"

a"

AA

!Aa"

aa"

A simple population genetics model"

AA

!Aa"

aa"

A"

a"

AA

!Aa"

aa"

If we know the frequency of allele A (i.e. p), then we can calculate

the expected genotype frequencies in the next generation"

(sperm)"

A"
(egg)"

a"

A"
AA"

a"
Aa"

Aa"

aa"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

Aa"

aa"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

P
"

p (1-p)"
"

Aa"

aa"

(1-p) p!
"

(1-p)2"

2!

"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

P
"

p (1-p)"
"

2!

Aa"

aa"

(1-p) p!
"

(1-p)2"
"

Offspring proportions"

AA
p2

!Aa
!2

!aa"

p(1-p) !(1-p)2"

!Q

!R"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

P
"

p (1-p)"
"

2!

Aa"

aa"

(1-p) p!
"

(1-p)2"

Offspring proportions"

AA
p2

!Aa
!2

"

So what is the allele frequency in the next generation?"

!aa"

p(1-p) !(1-p)2"

!Q

!R"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

P
"

p (1-p)"
"

2!

Aa"

aa"

(1-p) p!
"

(1-p)2"

Offspring proportions"

AA
p2

!Aa
!2

"

So what is the allele frequency in the next generation?"

p!=!D+H/2"
=!p2 +![2 p(1-p)]/2"
=!p2 +!p (1-p)"
=!p2 +!p - p2"
=!p (p+1-p)"
=!p!

!aa"

p(1-p) !(1-p)2"

!Q

!R"

(sperm)"
p!

p!

(egg)"

1-p!

A"
a"

1-p!

A"
AA"

a"
Aa"

P
"

p (1-p)"
"

2!

Aa"

aa"

(1-p) p!
"

(1-p)2"

Offspring proportions"

AA
p2

!Aa
!2

!aa"

p(1-p) !(1-p)2"

!Q

!R"

"

So what is the allele frequency in the next generation?"

p!=!D+H/2"
=!p2 +[2 p(1-p)]/2"
=!p2 +p (1-p)"
=!p (p+1-p)"
=!p!
Genotype frequency can change but allele frequency does not change over time"
Once in equilibrium both stay constant"
"

Hardy-Weinberg equilibrium"

The foundation on which almost all of the theory of

population genetics is based"

If the genotype frequencies are away from the H-W

equilibrium, in a single generation they regain it"
"
"
At equilibrium both genotype and allele
frequencies remain constant over time"

Hardy-Weinberg equilibrium"
However it is based on major assumptions of"
"
> No selection "
> Random mating"
> Infinitely large population"
> No disturbance to the gene pool (migration, mutation, recomb.) "
> All individuals have equal probabilities of survival, reproduction"

Hardy-Weinberg equilibrium"
Is it then even useful?"

Hardy-Weinberg equilibrium"
Is it then even useful?"

Is the scarlet tiger moth population in

H-W equilibrium?

E. B. Fords 1971 data"

White spotted (A1A1)
1469

Intermediate (A1A2)
138!
!
!
!

Little spotting (A2A2)"

5"

"
Total # of alleles: 1612"

Genotype frequencies:"

A1A1 = D = 1469/1612 = 0.911"

A1A2 = H = 138/1612 = 0.085"
A2A2 = R =
5/1612 = 0.004"
!!
!
1.000 "
"
"

E. B. Fords 1971 data"

White spotted (A1A1)
1469

"

Intermediate (A1A2)
138!
!
!
!

Genotype frequencies:"

Allele frequencies:"
A1A1

Little spotting (A2A2)"

5"

A1A1 = D = 1469/1612 = 0.911"

A1A2 = H = 138/1612 = 0.085"
A2A2 = R =
5/1612 = 0.004"
!!
!
1.000 "
"
" Total number of alleles in population

+ A1A2"

p(A1) = (2 x 1469 + 138)/ (2 x 1612) = 0.954"

q(A2)= (2 x 5 + 138)/ (2 x 1612)
= 0.046"
!! !
!
1.000 "
"
A2A2
+ A1A2"
"

Calculate expected genotype frequencies

under H-W principle "
Allele frequencies:"
p(A1) = (2 x 1469 + 138)/ (2 x 1612) = 0.954"
q(A2)= (2 x 5 + 138)/ (2 x 1612)
= 0.046"
!! !
!
1.000 "
"
"

Genotype frequencies
AA Aa
aa
p2 2pq q2
Expected f 0.91
0.09
0.002
Expected no. 1467 145 3
(f x no of ind.)

Observed

1469

138

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"

AA"

Offspring
Aa"

aa"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH
H2"
HR
DR"
HR
R2"

AA"

Offspring
Aa"

aa"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH
H2"
HR
DR"
HR
R2"

AA"
D2"

Offspring
Aa"

aa"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH
H2"
HR
DR"
HR
R2"

AA"
D2
DH/2"

Offspring
Aa"
"
DH/2"

aa"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH "
H2"
HR
DR"
HR "
R2"

AA"
2"

D
DH/2"
"
DH/2"
H2/4"

Offspring
Aa"

aa"

"
DH/2"
DR"
DH/2"
H2/2"
HR/2"
DR"
HR/2"
"
H2/4"
R2"
"
HR/2"
R2"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"

AA"
2"

D2"
DH
DR"
DH "
H2"
HR
DR"
HR "
R2"

D!=!D2+DH/2+DH/2+H2/4

D
DH/2"
"
DH/2"
H2/4"

Offspring
Aa"

aa"

"
DH/2"
DR"
DH/2"
H2/2"
HR/2"
DR"
HR/2"
"
H2/4"
R2"
"
HR/2"
R2"

!"
Remember
p = D+H/2"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

Mating
probability"

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

D!=!D2+DH+H2/4!"
=!(D+H/2)2 "
= !p2"

D2"
DH
DR"
DH "
H2"
HR
DR"
HR "
R2"

AA"
2"

D
DH/2"
"
DH/2"
H2/4"

Offspring
Aa"

aa"

"
DH/2"
DR"
DH/2"
H2/2"
HR/2"
DR"
HR/2"
"
H2/4"
R2"
"
HR/2"
R2"
Remember
p = D+H/2"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH "
H2"
HR
DR"
HR "
R2"

AA"
2"

D
DH/2"
"
DH/2"
H2/4"

p2"

Offspring
Aa"

aa"

"
DH/2"
DR"
DH/2"
H2/2"
HR/2"
DR"
HR/2"

"
H2/4"
R2"
"

HR/2"
R2"
2!p(1-p)" (1-p)2"

Alternatively"

Parents"
AA
AA
AA
Aa
Aa
Aa
aa
aa
aa

!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"
!AA"
!Aa"
!aa"

Mating
probability"
D2"
DH
DR"
DH "
H2"
HR
DR"
HR "
R2"

AA"
2"

D
DH/2"
"
DH/2"
H2/4"

p2"

Offspring
Aa"

aa"

"
DH/2"
DR"
DH/2"
H2/2"
HR/2"
DR"
HR/2"
2pq!

"
H2/4"
R2"
"
HR/2"
R2"
q2"

Hardy-Weinberg equilibrium"
This is the null hypothesis"
"
If this is not satisfied then it means
that probably something interesting
is happening!!"

e.g. non-random mating,"

or selection,"
or migration etc!

Summary"
Genetic and Environmental (as well as epigenetic)
processes drive the variation in populations"
Hardy-Weinberg equilibrium is a fundamental
concept of population genetics"
The H-W equilibrium will hold true only if a number
of assumptions are met"
These assumptions are expected to be violated in the
real world thus leading us to interesting phenomena"

"I have never done anything 'useful'. No discovery of mine has made, or is likely to make, directly or
indirectly, for good or ill, the least difference to the amenity of the world. - Hardy, G. H. (2004) [1940].
A Mathematician's Apology. Cambridge: University Press."