Slides 404 chp08 2023

evolution in finite populations:
drift, mutation and selection

evolution
chapter 08
1
outline
• the drift process • mutation, drift and
– the Wright-Fisher model selection
– change in heterozygosity • the neutral theory
– effective population size – why most substitutions
• the coalescent are neutral
– randomness of gene – the null model of
genealogies molecular evolution
• drift and demographic – (tests for positive
selection)
history
– bottlenecks and founder • the molecular clock
effects – variability in clock rates
2
loss of heterozygosity during
out-of-Africa
3
http://www.sciencemag.org/cgi/content/abstract/319/5866/1100
loss of heterozygosity during
out-of-Africa
• why does human pop heterozygosity

decrease farther away from Addis Ababa?
4
why do species differences
accumulate linearly with time?
5
weird alleles in isolated
populations
6
populations
7
http://slideplayer.com/slide/4659685
populations
• Ellis-van Creveld syndrome: dwarfism &
polydactyly
• 1/100,000
• but 6% in US Amish
8
https://www.nature.com/articles/ng0300_203
populations
• how can (slightly) deleterious variants become

so common?
– not just expressed due to inbreeding
9
Wright-Fisher populations
• like HW, no selection, no mutation, no
migration, random mating…
• but drift as a function of N – the effective

population size = number of breeding
individuals
10
11
• random sampling with replacement
• some alleles chosen multiple times (because
we assume the infinite gamete pool)
• and some never
12
WF exercise
• exercise: if N = 10 and pA1 = 0.1
– i.e. single copy
• P [loss of A1] in one generation ?
• exercise: if N = 10 and pA1 = 0.5

• P [loss of A1] in one generation ?
13
genetic drift
• random fluctuation of allele freqs across
generations
• reason: sampling error, but not bias

• e.g. early death or extra offspring unrelated to
the genotype
• selection would be a force that creates bias as a
function of the genotype
14
genetic drift
• drift, the sole force on neutral alleles
– causes increase & decrease, loss or fixation
– eventually one of the neutral alleles will fix
– but fixation by drift will take longer than by
selection
• but affects all alleles (neutral or under
selection), weakly or strongly
– depending on s (selection) and N (pop size)
15
genetic drift: random changes
• we cannot predict whether a neutral allele

increases or decreases in the next generation
– 50% chance each
– drunkard’s walk analogy
https://www.quora.com/What-is-a-
16
random-walk
drifting variants
17
Hamilton, Pop. Gen.
drift experiments in a small
population
• would the results differ at larger N?

18
what does the rate of drift
depend on?
• depends on pop size (N)

• small N à fast drift
• and for neutral allele A1 with

p, what is expected p'
19
what is expected p' ?
• expectation = average of all
possibilities
• expected p' = p
• both alleles have equal
chance to increase or
decrease
• …and the probability of

fixation of A1?
20
what is the probability of fixation
by drift?
• for neutral allele A1 with p :
• P[fixation of A1] = frequency

of A1 = p
21
what is the probability of fixation
by drift?
• P[fixation of A1] = frequency of A1
• assume a pop with all alleles unique: A1 … A2N

• then, fixation probability of A1 = 1/2N
• following this logic, if there exist k copies of A1

à fixation probability of A1 = k * 1/2N = p
22
exercise: fixation probability of a
neutral allele
• a neutral allele at frequency 70% à what is its
probability of fixation?
• a beneficial allele at frequency 70% à what is
its probability of fixation (more or less than
70%)?
• … and so, how will drift affect heterozygosity

(H) in a population in the long run?
23
drift, inbreeding, heterozygosity
• in the long term: drift decreases H, increases
homozygosity à causes loss or fixation of
alleles
• in the short term: drift can lead to temporary
increase in H
• but on average, it tends to create

homozygous individuals that carry IBD
alleles (F can also measure drift) - how?
24
• assume no drift ~ inbreeding in the past
• assume all 2N alleles unique à Ft=0 = 0, then?
• what is F in the next generation?

– i.e. what is P[IBD of 2 randomly chosen alleles] ?
25
• assume all 2N alleles unique à Ft=0 = 0, then?
• Ft=1 = 1/2N
• à chance that the same allele is chosen twice
26
• imagine a WF pop of 2 diploid indv, with 4 alleles:
• A1, A2, A3, A4
• F = chance of an individual being homozygous
• Ft=0 = 0
• to create the next generation, imagine an infinite
gamete pool, each allele represented by its
frequency
• if we choose one A1, what is the chance we
choose A1 again to create a homozygous
individual? à Ft=1 = 1/4
27
• so the expected Ft=1 = 1/2N
• the empirical Ft=1 will vary around this value
• but if we repeat this experiment many times

can calculate the average (i.e. the
expectation): Ft=1 = 1/2N
• how will F change over many generations?

28
• assume all 2N alleles unique à Ft=0 = 0
29
• F increases by 1/2N each generation via drift
30
• so, offspring F:
• F' = (1 - 1/2N)*F + 1/2N
• how will F change in the long run?

• how will heterozygosity change?
• what is the equilibrium?
31
how much will heterozygosity
change?
• small N à faster change in H

• conversely, if N is infinite, no change in H
• so change in H informs about N
32
• if no other effect, equilibrium H = 0
• so what restores H in real populations?
• à de novo mutations (plus gene flow)
33
why is drift important?
• drift changes allele freqs all the time
• drift signatures inform about past population
sizes = demographic history
• drift shapes population and species
divergence at the molecular level, and
possibly also at the phenotypic level
• drift can facilitate speciation
34
why is drift important?
• drift can change allele freqs against selection,
which may be harmful for a pop:
• e.g. losing recessive beneficial alleles, or fixing
slightly deleterious variants
• drift can explain important biological
phenomena, like ageing
• drift can also help avoid getting stuck at local
adaptive fitness peaks
35
how to measure drift?
• drift a function of pop size, N

• but would N be all individuals in a pop?
36
effective population size (Ne)
• case study: change in H measured in fish:

indicates N < 200
• but fish absolute pop size = 3e6
• how possible?
37
• Ne: breeding indv number

• Ne determines drift rate à if small à drift fast
• actual (census) pop size does not matter
38
• Ne can be measured by:
• change in heterozygosity : higher Ne à slower
change
• genetic diversity (or drift) : higher Ne à higher
diversity – why?
• 1) slower drift + 2) higher mutations every
generation
• diversity levels more commonly used for Ne
estimation
39
why is usually Ne < census size ?
• because Ne represents past breeders
• breeders: a subset of living individuals +
• periods of past bottleneck can decrease Ne
• e.g. today, human Ne ~10,000 indv, while chimp
Ne ~20,000 indv
• reflects small human population from >200,000
years ago
40
past bottlenecks reduce Ne
• when N fluctuates in time (m generations) à
long term Ne determined by the harmonic
mean à influenced by smaller values
• à Ne closer to bottleneck values

41
42
Hamilton, Population Genetics
• if N = 100,000 for 95 generations, and N = 50
for only 5 generations, what is Ne?
43
sex-bias in breeding reduces Ne
• Ne also reflects the average of male and
female breeder numbers
• equations derived elsewhere (e.g. Hamilton,

Population Genetics, pg 97)
44
sex-bias in breeding reduces Ne
• what is Ne if 10 male and 300 female gorillas
are breeding?
• Ne = (4*300*10)/310 ~ 40
45
drift and pop divergence
• if two populations split (become isolated),
how will drift affect their similarity?
• genetic drift experiment – how to design?
46
• drift experiment with fruit fly
• start at 50% freq of a white eye allele
• randomly choose 8 males + 8 females in
each population
• change?
47
48
49
microsatellite (STR) diversity in
Galapagos lizards
50
microsatellite (STR) diversity in
Galapagos lizards
• small vs large islands differ in allelic diversity

• islands also differ in allele frequencies among
themselves
• à both are results of drift 51
gene genealogies
• species / population tree vs. gene tree
• gene genealogy: traces the ancestry of gene
copies (i.e. loci)
• in eukaryotic species with meiosis, each locus
has a different history
– individuals are mosaics of different loci with
different histories
• coalescence: a model for studying gene
genealogies
52
coalescence
• coalescence of gene copies in a gene tree =
two gene copies at generation t originating
from a single copy (IBD) at generation t-1
• coalescence represents drift, but backwards

in time
• it’s a stochastic process, modeled by Poisson

53
coalescence
54
coalescence
55
coalescence
• if we go far enough back, how many ancestors
of a locus with n=10 copies today?
56
coalescence
• if we go far enough back, how many ancestors
of a locus with n=10 copies today?
• just one
– remember that at each locus, one allele will
eventually fix
– e.g. human “mitochondrial Eve” lived about 200k
years ago
– how about human "Y-chr Adam"?
57
average time to coalescence?
• the average time to coalesce for a pair of
gene copies in a diploid species with pop size
N?
58
• coalescence is a Poisson event
• = coalescence probabilities modeled by the
Poisson distribution
• à average waiting times for coalescence are
exponentially distributed
59
• random event with probability P à average
waiting time = 1/P
– e.g. 2 individuals having the same birthday: 1/365
à on average you need to find 365 individuals to
find a pair with same birthday
• probability of 2 alleles having the same
ancestor in the previous generation = 1/2N
• assuming fixed population size
• average waiting time for coalescence = 2N
generations 60
average time to coalescence
• the average time to coalesce for a pair of gene
copies in a diploid species with pop size N:
• 2N
• the average time to coalesce for all gene

• 4N
– derived in Box 8.4
61
• waiting time shortens with more gene copies
= possible combinations that may coalesce
within a certain time
62
• the average time to coalesce for all gene
• 4N = average time to fixation (by drift),

starting from a single gene copy
– e.g. if Ne = 100,000 à time to fix for a de novo
mutation = 400,000 gen
63
• comparing between pop with small vs. large
Ne à coalescence faster (= fixation faster)
with small Ne (i.e. faster drift)
64
coalescence times for different loci
• simulations under the same Ne:
• coalescence times stochastic

• high variance in coalescence times in a pop
across loci
65
gene trees vs species trees
• trees of individual loci sometimes might not

reflect the species tree
https://journals.plos.org/plosgenetics/article/figure?id=10.1 66
371/journal.pgen.0020068.g001
how many differences between 2 gene
copies at a neutral locus?
• how many differences expected between 2

randomly drawn gene copies at a neutral
diploid locus?
1. depends on when they coalesced

2. depends on how many mutations happened
• both are stochastic processes

67
how many differences between 2
gene copies at a neutral locus?
68
69
• for 2 copies at a neutral diploid locus: average

time to coalesce = 2N
• total time in tree (considering both branches)

= 2N + 2N = 4N generations
70
• μ = mutation rate per generation
• expected number of mutations between 2
copies at a neutral diploid locus
= time x mutation rate
= 4Nμ
• so, higher Ne à higher diversity
(heterozygosity)
• given diversity & μ à we can estimate Ne
71
coalescence / drift at different loci
• in eukaryotes doing meiosis, each locus has a
different drift history
– we are all mosaics of ancestral genes
• the history of loci with different transmission
modes can be even more different
• drift in mitochondria vs. autosomal loci vs. X

chr loci à how will they differ?
72
• assuming equal numbers of males and
females:
• autosomal Ne ~ 4 * mitochondrial Ne
• X chr Ne ~ 3 * mitochondrial Ne
• slowest drift = longer coalescence times at
autosomes
• faster drift = shorter coalescence times in
mitochondria à less diversity within pop,
more divergence between pop
73
• e.g. human “mitochondrial Eve” (most recent
common ancestor) lived ~ 200kya
• no recombination
• did there exist a “nuclear Eve” as well?

• when did it/they live? earlier or later?
74
coalescence, mutation, selection
75
coalescence, mutation, selection
• coalescence fast under positive selection
(relative to neutral loci)
– faster coalescence = recent ancestry = fewer
variants can accumulate (relative to neutral) à
regions under positive selection will have less
genetic diversity (relative to neutral)
• coalescence slow under balancing selection
(relative to neutral loci)
– more polymorphism than neutral
76
bottlenecks & founder effects
• cases of extreme drift
• reduce diversity in the population
• all copies coalesce at bottleneck time
• lost diversity cannot be regained for long
periods, even if pop size increases
– because mutation is a slow event
77
78
79
80
hunted seals
• Northern elephant seals hunted intensely in the

past, but the population has later recovered in
numbers à any consequences of bottleneck?
81
82
83
bottlenecks can support speciation
rapid
coalescence at
bottleneck
loss of self-
incompatibility
à bottleneck à
differentiation
à speciation
84
https://www.pnas.org/content/106/13/5246
human migrations out-of-Africa
85
human migrations out-of-Africa
X
X
86
Zimmer 2013 The Tangled Bank
• out-of-Africa
branches
longer than
African
branches
• Americas even
longer
• why?
http://www.sciencemag.org/cgi/content/ab
87
stract/319/5866/1100
• drift: alleles fix
during
founder
effects à
differentiate
those
populations
from others
http://www.sciencemag.org/cgi/content/ab
88
stract/319/5866/1100
founder effects in spruce
89
• will mtDNA or autosomes be more affected by

possible founder effects in spruce?
90
• mtDNA
diversity
limited in
newly
colonized
regions
91
mutation-drift equilibrium
• F = probability of IBD w/o mutation
• every generation:
• F increases by 1/2N by drift
• F decreases by μ (mutation)
• F at equilibrium?
92
• F at equilibrium?
93
• at equilibrium: Foffspring = Fparental
94
• probability of homozygosity of 2 gene copies:
!
𝐹equilibrium =
"#$%!
– (can also be calculated as the probability of
coalescence happening before mutation)
• expected number of differences between 2
gene copies: 𝐻 = 4𝑁𝜇
"#$
• Heterozygosity = 1 − 𝐹equilibrium = "#$%!
• as 4𝑁𝜇 à 0, Heterozygosity à 4𝑁𝜇
95
selection vs. drift
• fate of new alleles (= rare alleles): determined
by drift, even if beneficial
• why? the number of offspring per parent is

limited à beneficial alleles can be lost
– e.g. a human mother carries a beneficial allele
where s = 0.1 – how many offspring is she
expected to have, if average mums have 2
offspring?
96
selection vs. drift
• fixation probability P of a
single copy beneficial (and
partial dominant) allele, in a
large population (JBS
Haldane)
• fitness = 1 + s
• P[fixation of beneficial
allele] = 2s
97
selection vs. drift
• P[fixation of a de novo beneficial allele] = 2s
• if s = 5% à P = 10%
• if s = 1% à P = 2%
• so, many beneficial alleles lost at early stage
• even more lost if beneficial alleles are
recessive
• compare with P[fixation of a neutral allele] =

1/2N
98
selection vs. drift
• assume the beneficial allele reached 1% freq
• still, no guarantee of fixation if drift is strong
and s is weak
• selection dominates over drift only when:
• s > 1/2Ne (M Kimura)
99
selection vs. drift
starting at
1% freq
100
selection vs. drift
101
selection or drift?
• 1930’s: patterns of diversity and divergence

assumed to be due to selection (drift not
considered)
• e.g. genetic variation assumed exceptional à
“selection should rapidly remove variation”
• polymorphism assumed to indicate balancing
selection
102
selection or drift?
• 1960’s: protein isoform polymorphism studied

in natural populations (R Lewontin)
• à much more variation than expected –
why?
• due to balancing selection, or some simpler
explanation?
103
a neutral explanation
• most genetic diversity within populations

(DNA or protein) is neutral
– the main source of diversity is not balancing
selection but, mutation + drift
• most divergence between populations /
species, also neutral
– the main source of interspecies divergence is not
directional selection but, mutation + drift
104
a neutral explanation
• many de novo functional mutations

deleterious
• but most observed DNA variations, both
within pop or between species, are neutral or
close to neutral
105
fitness effects
these can drift to high
frequencies and contribute to
polymorphism and fixation
106
neutral theory of molecular evolution
• in nature, molecular diversity & divergence
mainly shaped by:
– mutation
– negative selection
– neutral drift
– directional selection also contributes to
divergence, and balancing selection contributes to
diversity, but both at lower levels than mutation
and drift
• how come most substitutions neutral?
107
how come most substitutions neutral?
• in many eukaryotes most DNA is non-coding
& non-functional
• coding region variants can be synonymous
(degeneracy of the code)
• functional (non-synonymous or regulatory)
variants may have no effect on fitness
• selection can be ineffective when Ne and/or s
are small
– e.g. deleterious mutations can behave like
neutral 108
most substitutions synonymous
• observation: most nucleotide substitutions in

coding regions are synonymous
• warning: not mutations, but substitutions
• (most 3rd position substitutions synonymous)

109
most substitutions synonymous
• non-synonymous / total substitution rate for

800+ mouse-rat gene pairs
110
many non-synonymous changes can
also be neutral
• even many non-synonymous changes can be
neutral
• human-rat-chicken
comparison of
TRPV
111
how come most substitutions neutral?
• non-coding regions (intronic and intergenic):

– transposons
– simple repeats
– pseudogenes (deactivated genes)
• L-gulono- gamma-lactone oxidase – VitC synthesis
112
strength of selection depends on 2Nes
• if for a functional mutation 2Nes < 1: natural

selection cannot see it
• the mutation is effectively neutral in that

population
113
• e.g. in Neanderthals Ne = 1,000

• s < -0.001 effectively neutral
• à slightly bad alleles can drift to fixation in
Neanderthal, but not so easily in human, and
even less in mouse http://www.genetics.org/content/203/2/881.long
114
• the composition of functional substitutions
(divergence): depends on N
– in species with large N: majority of functional
substitutions may have been positively selected
• e.g. Drosophila
– in species with small N: minority of functional
substitutions positively selected
• e.g. human
115
neutral theory of molecular evolution
• neutral theory = (drift + negative selection) à

null model
• positive selection à alternative model
• we can study selection by testing neutrality à

can be rejected, selection (positive selection =
adaptive evolution, purifying selection, or
balancing selection) can be inferred
116
molecular clock
• 1960s:
• molecular divergence ~ divergence times
estimated from the fossil record
117
molecular clock
• 1960s:
• equidistance principle:
outgroup-A distance =
outgroup-B distance
• à rate of substitution
similar among
branches, in general
118
molecular clock
• equidistance principle
• but shouldn't large

populations gain more
mutations per generation
than small populations?
• how do they evolve at the
same rate?
119
molecular clock
• large populations gain
more mutations per gen
• small populations fix
more mutations (by drift)
per gen
• remember the case of
founder effects in human
populations
120
molecular clock
• k neutral loci, N pop size, μ mutation rate
• 2Nkμ neutral mutations arise each gen
• 1/2N fix
• the rate of new alleles becoming fixed:
• substitution rate = 2Nkμ * 1/2N = kμ
• N not a factor in neutral substitution rate à
molecular clock
121
molecular clock
• use mutation rate per time for a DNA/protein
sequence à calculate the time since the most
recent common ancestor (TMRCA) of 2 taxa
• mutation rate calculated using fossil data +

DNA difference data for species A and B
– for which we have good fossil data
• TMRCA age for species C and D estimated

using this rate & DNA differences between C
and D 122
molecular clock
https://evolution.berk
eley.edu/evolibrary/ar
ticle/molecclocks_01
• e.g. fossil data: TMRCA of A and B lived 50 mya

• we find in total 4 substitutions between their DNA
sequences at locus X
• à4/2 = 2 events must have happened in each lineage
• à mutation rate for locus X = 1 substitution / 25 mya
• for species C and D: if we observe 6 substitutions at
locus X, what is their TMRCA? 123
molecular clock
https://evolution.berk
eley.edu/evolibrary/ar
ticle/molecclocks_01
• for species C and D: if we observe 6 substitutions at

locus X, what is their TMRCA?
• 6/2 = 3 substitutions per lineage
• 3 subs / (1 subs/25 mya) = 75 mya
124
does the clock always tick
perfectly?
• early studies: protein divergence appears
linear
• but does the clock always tick perfectly?

125
does the clock always tick
perfectly?
• clock rate will vary, possibly depending on:
o mutation rate
o selection (both negative & positive)
o saturation (time since divergence)
o generation time
126
some genome regions have higher
mutation rate
• in primates: neutral regions in mtDNA evolve

5-10x faster than neutral regions in nuclear
DNA
• ß due to high mutation rate in mitochondria
in animals
127
loci under purifying selection
evolve slower
• influenza A: the effect of negative selection
128
loci under positive selection evolve
faster
• two loci in HIV – which locus is under pos and
which one negative selection?
129
sequence divergence may saturate
with time
130
transitions saturate faster than
transversions - why?
131
which loci to use for
molecular clock analyses?
• recent events may be timed using:

– synonymous substitutions (at 3rd codon positions)
– loci with high mut rate (mtDNA, STRs)
– silent and/or neutral loci (e.g. pseudogenes,
mtDNA control region)
à these will give resolution but also saturate fast
132
which loci to use for
molecular clock analyses?
• old events may be timed using:

– missense substitutions (accumulate slow)
– transversions (slower rate)
– highly conserved genes (e.g. 16S ribosomal RNA,
“housekeeping genes”, cytochrome C)
– e.g. 16S ribosomal RNA: ~50 million years per 1%
sequence divergence
133
molecular clock
• clock rate will vary, possibly depending on:
o mutation rate
o selection (both negative & positive)
o saturation (time since divergence)
o generation time
• à one may use relaxed molecular clocks,

controlling for these effects
134
applications to experiment with
• drift and selection
• https://cjbattey.shinyapps.io/driftR/
– try drift, directional selection, balancing
selection, drift and selection, study time to
fixation of a neutral allele
• coalescence
• https://cdmuir.shinyapps.io/coalescence/
135
additional slides
136
generation time and the molecular
clock
• rodent branches not 50x longer than primate
branches – why?
137
http://www.nature.com/nature/journal/v437/n7055/full/nature04072.html
clock
• divergence correlated with more time (years)
than with number of generations
138
clock
• generation time has limited effect – why?
• nearly neutral theory (Ohta)
139
clock
140
clock
• in species with long gen time + small N:
• slightly deleterious mutations à effectively
neutral à can fix and accumulate by drift
• in species with short gen time + large N:

• slightly deleterious mutations cannot accumulate,
but neutral mutations accumulate fast
• the effects balance each other out à linear

change over time
141
clock
• with more molecular data
• + more fossil data
• better understanding of the molecular clock
process
142
WF model simulations in R
143
144
N <- 1000
p <- 0.2
gens <- 2000
x <- rep(c(1,0), times = c(p,(1-p))*N)
freqs <- mean(x)
for (i in 2:gens) {
x <- sample(x, rep=T)
freqs[i] <- mean(x)
}
plot(freqs, type="l", ylim=c(0,1), xlab="Generation", ylab="Frequency",
main=paste("p =", p, "; N =", N))
145
N <- 300
p <- 0.2
gens <- 2000
sims <- 20
sim <- sapply(1:sims, function(j) {
x <- rep(c(1,0), times = c(p,(1-p))*N)
freqs = mean(x)
for (i in 2:gens) {
x <- sample(x, rep=T)
freqs[i] <- mean(x)
}
return(freqs)
})
146
matplot(sim, type="l", ylim=c(0,1), xlab="Generation",
ylab="Frequency", main=paste(sims, "trials ; p =", p, "; N =", N))
147

Slides 404 chp08 2023

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Slides 404 chp08 2023

Uploaded by

Copyright:

Available Formats

evolution in finite populations:

drift, mutation and selection

• why does human pop heterozygosity

• how can (slightly) deleterious variants become

• but drift as a function of N – the effective

• exercise: if N = 10 and pA1 = 0.5

• reason: sampling error, but not bias

• we cannot predict whether a neutral allele

• would the results differ at larger N?

• depends on pop size (N)

• and for neutral allele A1 with

• …and the probability of

• for neutral allele A1 with p :

• P[fixation of A1] = frequency

• assume a pop with all alleles unique: A1 … A2N

• following this logic, if there exist k copies of A1

• … and so, how will drift affect heterozygosity

• but on average, it tends to create

• what is F in the next generation?

• but if we repeat this experiment many times

• how will F change over many generations?

• how will F change in the long run?

• small N à faster change in H

• à de novo mutations (plus gene flow)

• drift a function of pop size, N

• case study: change in H measured in fish:

• Ne: breeding indv number

• à Ne closer to bottleneck values

• equations derived elsewhere (e.g. Hamilton,

• small vs large islands differ in allelic diversity

• coalescence represents drift, but backwards

• it’s a stochastic process, modeled by Poisson

• the average time to coalesce for all gene

• 4N = average time to fixation (by drift),

• coalescence times stochastic

• trees of individual loci sometimes might not

• how many differences expected between 2

1. depends on when they coalesced

• both are stochastic processes

• for 2 copies at a neutral diploid locus: average

• total time in tree (considering both branches)

• drift in mitochondria vs. autosomal loci vs. X

• did there exist a “nuclear Eve” as well?

• Northern elephant seals hunted intensely in the

• will mtDNA or autosomes be more affected by

• why? the number of offspring per parent is

• compare with P[fixation of a neutral allele] =

• 1930’s: patterns of diversity and divergence

• 1960’s: protein isoform polymorphism studied

• most genetic diversity within populations

• many de novo functional mutations

• observation: most nucleotide substitutions in

• (most 3rd position substitutions synonymous)

• non-synonymous / total substitution rate for

• non-coding regions (intronic and intergenic):

• if for a functional mutation 2Nes < 1: natural

• the mutation is effectively neutral in that

• e.g. in Neanderthals Ne = 1,000

• neutral theory = (drift + negative selection) à

• we can study selection by testing neutrality à

• but shouldn't large

• mutation rate calculated using fossil data +