rDNA structure

The role of the IGS in the rDNA is mostly

unknown"

Phylogenetic footprinting
identified noncoding promoter

Characterisation of the
noncoding promoter
rDNA copy number
usually recovers if
some are deleted
The noncoding IGS
promoter is required
for this rDNA
amplification
Kobayashi & Ganley, 2005 Science 309: 1581-1584

Detecting positive selection

We will look at three methods for detecting
positive selection:"
More non-synonymous than synonymous
mutations (Dn/Ds ratio)"
Phylogenetic Dn/Ds ratio"
Selective sweeps"

dN/dS ratio redux

The reverse logic for the dN/dS ratio can be
used to find evidence for positive selection"
Under positive selection, you expect more
non-synonymous mutations than
synonymous mutations!
Therefore a dN/dS ratio of greater than 1
suggests positive selection"

Example: heterochromatin
protein 1 variant
Looking at a protein called heterochromatin
protein 1 (HP1), which functions in
specifying heterochromatin"
In Drosophila melanogaster there there are
five HP1 paralogs"
Found that one (HP1-rhino) showed
evidence of evolving via positive selective"
Suggests its involved in some aspect of
adaptation"

Example: HP1_rhino protein

Vermaack et al, 2005.
PLoS Genetics 1: e9

Other HP1 paralogs are evolving under negative selection,

but the HP1-rhino shows a high dN/dS ratio"

Limitations of dN/dS for

positive selection
Similar to those for the dN/dS ratio with
negative selection"
Only works on protein-coding regions of the
genome"
Has limited sensitivity typically only a few
sites are undergoing positive selection"
Need to take bias in mutations into account"

Phylogenetic dN/dS ratio

The dN/dS ratio averages over all evolution
that has occurred between species"
However, the positive selection may have
only occurred during one part of the
evolutionary history difficult to detect"
Therefore, phylogenetic approaches are
used to estimate the dN/dS ratios on each
branch of a phylogenetic tree"

Lineage-specific dN/dS
Maybe
positive
selection
only
occurred
in this
gene at
this point
in time?"

Ancestral state reconstruction

By recreating
the ancestral
sequences,
we can now
compare dN/
dS at each
point in the
phylogeny"

Limitations of phylogenetic
dN/dS for positive selection
Similar to those for the simple dN/dS ratio "
In addition, ancestral state reconstruction is
not simple, and the dN/dS relies on it being
accurate, which it might not be"

Selective sweeps
When a mutation is selected, it will take
along neighbouring SNPs that are linked"
This is called a selective sweep, and the
the neighbouring SNPs are said to
hitchhike along with the positively selected
mutation"
The extent of DNA that hitchhikes along with
the selected mutation is governed by
meiotic recombination"

 Involves
the
adaptive
allele
sweeping
to fixation
in the
population"
Normally,
this
happens
on an
ongoing
basis"

Selective sweeps
Positive
selection
for green
mutation

Neutral
evolution
and
selection
against red
mutations

Selective sweeps
Results in a
signature of
decreased
genetic
variation
around the
positivelyselected
mutation

Detecting selective sweeps

Selective sweeps can be detected by
scanning the genome in a population for
regions of low polymorphism/high linkage
disequilibrium"
However, limitations arise because other
factors can also result in this pattern"
In particular, variation in the rate of meiotic
recombination across the genome can
cause dramatic differences in the level of
linkage disequilibrium "

Horizontal gene transfer

One unusual way a genome can evolve is
by picking up bits from other species
genomes"
Known as horizontal gene transfer (HGT)
exchange of genetic material between non
parent-offspring individuals"
HGT is very common in bacteria they
seem to swap parts of their genome with
abandon but is much more controversial in
eukaryote evolution "

Horizontal gene transfer

Horizontal gene
Soucy ettransfer
al, 2015 Nature

Reviews Genetics 16: 472-482

Mitochondria/chloroplasts
Mitochondria and chloroplasts are examples
of HGT"
They are bacterial endosymbionts of
eukaryote cells"
In both cases many genes have been
horizontally transferred from mitochondria
and chloroplasts into the nuclear genome"
Because of the endosymbiotic relationship,
these are considered special cases"

Detecting HGT
The gold standard for detecting HGT is
phylogenetic incongruence"
When the phylogenetic tree for a region of
the genome disagrees with the established
species phylogeny"
Such incongruence is consistent with that
region having been horizontally transferred"
However, other explanations are possible:
e.g. frequent gene gains/losses, or rapid
evolution of a gene in one lineage"

 Urochordates (tunicates)
are marine invertebrates
with notochords (sea
squirts, etc)"
Only animals known to
have cellulose"
The gene encoding
cellulose synthase in Ciona
(a model urochordate)
groups with bacteria
cellulose synthases, and
not with eukaryote
enzymes"
Suggests the gene was
horizontally transferred
from bacteria into
urochordates"

Care is needed
The original paper describing the human
genome in 2001 found 113 genes that are
likely to have been horizontally transferred
to vertebrates from bacteria"
Based on BLAST searches where the
closest match outside of vertebrates was a
bacterial gene"

A more careful phylogenetic analysis showed a variety of

eukaryotes orthologs, thus none of these are HGT examples"

Long branch problems

A gene that is evolving quickly in one lineage but
not others will show up as a long branch in a
phylogenetic tree"

http://mesquiteproject.org/
mesquite1.0/Mesquite_Folder/
docs/mesquite/studies/
study002/index.html

Long branch problems

These often falsely group together in phylogenetic
trees, or otherwise end up in weird places"

Nested phylogenetic
incongruence: gold standard!
Problems like long branches mean simple
phylogenetic incongruence can be
misleading"
Therefore, convincing evidence for HGT:
the HGT recipient lineages nest within the
donor lineages, to the exclusion of other
lineages related to the recipient lineages"

Simple incongruence is
not enough

Gene X

species
phylogeny

This pattern could result from a variety of

causes, including, but not limited to, HGT"

Chou et al, 2015

Nature 518: 98-

HGT from bacteria to eukaryotes

Shows transfers
of antimicrobial
genes from
bacteria into
water fleas and
ticks"
Genes are
functional in
their eukaryotic
hosts, protecting
against bacterial
infection"

Final cool examples

HGT of genes involved in breakdown of
seaweed cell walls from algal parasites to
human gut microbes"
So far, only found in Japanese people,
giving them a unique ability to use seaweed
as a food source!"
Placental syncytin genes came from HGT of
viral genes into mammals"