Evolution and
Population Genetics
Xiaole Shirley Liu
STAT115 / STAT215
Evolution
• “Nothing in biology makes sense except in
the light of evolution”
– Theodosius Dobzhansky
2
Evolution
• Evolution is a gradual change in genetic makeup
from one generation to the next
• Evolution:
Nonrandom
• Natural Selection
process
• Mutation
Random
• Genetic Drift
processes
…
• Natural selection and genetic drift are the two most
important causes of allele substitution in populations
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Evolution
• Evolution creates species-specific and
population-specific differences
• Are they all selected for advantages to the
species or population?
Some definitions:
• Locus: position on
chromosome where a
sequence or a gene is located
• Allele: alternative form of
DNA on a locus
• Written as A vs a, or A vs B
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Natural Selection
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Phenotypic vs Molecular Evolution
• Phenotypic evolution is controlled by
natural selection
• Molecular mutations are selectively
neutral in the strict sense as that their
fate in evolution is largely determined by
random genetic drift
• Some evolutionary geneticists believe
that genetic drift should be the “null
hypothesis” used to explain an
evolutionary observation unless there is
positive evidence of natural selection
6
Motoo Kimura
Neural Theory and Genetic Drift
• Genetic drift as sampling error
• Selected (sampling) copies of an allele carry the
information to off springs that survive to reproduce
• Sampling is subject to random variation or sampling
error
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Random Fluctuation in Allele Frequencies
Metapopulation
Deme p q
Neutral alleles
pt
p'
…
time
• If there is no stabilizing force returns the allele
frequency towards ½, p will eventually drift either
to 0 or 1, i.e. the allele is either lost or fixed in
each sub-population
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Allele Frequency Analogy to Random Walk
Traveler staggering along a long train platform with a railroad
track on either side: if he is so drunk that he does not
compensate steps towards one side with steps towards the
other, he will eventually fall off the edge of the platform onto
one of the two tracks
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Coalescence
• The genealogy of the genes in
the present population is said to
coalesce back to a single
common ancestor
• The overall heterogeneity of a
population will decrease
• By chance, a population will
eventually become
monomorphic for one allele or
the other
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Genetic Drift
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• Deme: a subdivision of a population consisting of
closely related plants, animals or people, typically
breeding mainly within the group.
• Initial mutation (allele) occurs in a deme of N
individuals
• Assuming neutral evolution, its probably of being
sampled in the offspring is
1/2N
• Over time, allele frequency
will fluctuate, population
diversity will decrease till
allele fix or lost
Genetic Drift
• Effect of population size N (N is actually called
effective population size)
• The likelihood of a mutation being fixed is its
initial frequency (1 / 2N): it is more likely to be
fixed in a small deme than in a large deme
Metapopulation
Deme p q
Neutral alleles
pt
p'
…
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time
Genetic Drift
• An allele’s probability of fixation equals its
frequency at that time and is not affected by its
previous history
• In a diploid population, the average time to
fixation of a newly arisen neutral allele that does
become fixed is 4N generations: evolution by
genetic drift proceeds faster in small than in large
populations
• Demes that initially are genetically identical
evolve by chance to have different genetic
constitutions
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Evolution by Genetic Drift
• Among a number of initially identical demes in a
metapopulation, the average allele frequency does
not change but the frequency of heterozygotes
declines to 0 in each deme
Metapopulation
Deme p q
Neutral alleles
pt
p'
…
14
time
Founder Effect
• Random genetic drift that ensues the
establishment of a new population by a
small number of colonists
What would one
expect from the
formation of new
populations by just a
few individuals?
Ellis–van Creveld
syndrome in Amish
population
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Founder Effect
• If the colony rapidly grows: allele frequencies will
not be greatly altered from those in the source
population although some rare alleles will not
have been carried by the founders
• If the colony remains small: genetic drift will alter
allele frequencies and erode genetic variation 
move quickly towards fix or lost
• If the colony persists and grows: new mutations
eventually restore heterozygosity to higher levels
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The Neutral Theory of Molecular Evolution
• 1.1. Minority of mutations are advantageous
(fixed)
• 1.2. Many mutations are disadvantageous
(eliminated)
• 1.3. Treat majority of mutations that are fixed are
effectively neutral from genetic drifts
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The Neutral Theory of Molecular Evolution
•
•
•
•
1.1. Minority of mutations are advantagous
1.2. Many mutations are disadvantageous
1.3. Treat majority of mutations effectively neutral
2. Most genetic variation at the molecular level is
selectively neutral and lacks adaptive significance
• 3. Evolutionary substitutions at the molecular level
proceed at a roughly constant rate so that the
degree of sequence difference between species can
serve as a MOLECULAR CLOCK
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By comparing DNA changes among
populations we can trace their history
Population 1:
Population 2:
Population 3:
Population 4:
1
ATGTAACGTTATA
ACGTAACGTTATA
ACGAAACGTTATA
ACGAAACCTTATA
2
3
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From Phylogeny to Selection
• The protein-coding portion of DNA
has synonymous and nonsynonymous
substitutions. Thus, some DNA changes do not
have corresponding protein changes.
• If the synonymous substitution rate (dS) is greater
than the nonsynonymous substitution rate (dN),
the DNA sequence is under negative (purifying)
selection.
• If dS < dN, positive selection occurs. E.g. a
duplicated gene may evolve rapidly to assume
new functions.
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The Neutral Theory of Molecular Evolution
•
•
•
•
1.1. Minority of mutations are advantagous
1.2. Many mutations are disadvantageous
1.3. Treat majority of mutations effectively neutral
2. Most genetic variation at the molecular level is
selectively neutral and lacks adaptive significance
• 3. Evolutionary substitutions at the molecular level
proceed at a roughly constant rate so that the
degree of sequence difference between species can
serve as a MOLECULAR CLOCK
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Molecular Clock
• If protein sequences evolve at constant rates, they
can be used to estimate the times that sequences
diverged. This is analogous to dating geological
specimens by radioactive decay.
• L = number of nucleotide sites compared between
two sequences
• N = total number of substitutions
• K = N / L, number of substitutions per nucleotide
site
• K = 0.093 for rat versus human
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Graur and Li (2000)
Molecular Clock
• r = rate of substitution (mutations) = 0.56 x 10-9
per site per year
• r = K / 2T  T = .093 / (2)(0.56 x 10-9) = 80
million years
Over a sufficiently long time
some sites experience repeated
base substitutions, so the
observed number of differences
will plateau.
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Graur and Li (2000)
Where did we come from?
• Two competing hypotheses
– Multiregional evolution (1 millions years ago, Homo erectus
left Africa, and evolve into modern humans in different parts
of the Old World)
– The Out of Africa hypothesis: Homo erectus were displaced
by new populations of modern humans that left Africa 100K
to 50K years ago.
Modern humans
Europe
Africa
Homo erectus
Africa
Asia
Modern humans
Europe
Africa
Homo erectus
Africa
Asia
• National Geographic Story
• If a fragment of DNA is shared by Neanderthals
and non-Africans, but not Africans or other
primates, it is likely to be a Neanderthal heirloom.
• People living outside Africa carries 1-4% of
Neanderthal DNA (skin, hair, etc).
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Summary
• Phenotype evolution (natural selection) vs
molecular evolution (neutral theory)
• Genetic drifts from sampling error
• Decrease of genetic variation over time
• Probability of fixation depends on frequency
• Population size influence speed of fixation
• Founder’s effect
• Positive and negative selection (dN / dS ratio)
• Molecular clock and migration patterns
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Acknowledgement
• Francisco Ubeda
• Jun Liu
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