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23 Popula+on Gene+cs and

R. Lewontin The Genetic Basis of Evolutionary Change.
Columbia University Press 1970. !
Darwin called attention to the actual variation among actual
organisms as the most essential and illuminating fact of nature
.the Darwinian view that evolution begins with the conversion
of variation between individuals into variation between
populations, the divergence of populations partly or wholly
isolated from one another.!

Varia+on and Evolu+on

In the absence of
natural selec+on, non random breeding
and small popula+on sizes (founder eects
and dri7) substan+al migra+on and
muta+on, the randomiza+on of sex will
keep sexual popula+ons in gene+c
equilibrium indenitely

A, contemporary example of how within-popula+on varia+on (body

size, behaviour and beak morphology) is being converted to between-
species varia+on, through (1)isola+on (2) access to diverse unexploited
resources (3)selec+on imposed by environmental change

Selec+on modeled as
a quan+ta+ve
R= h2S'

The Galapagos, home of the Galapagos nches

Se B.R. Grant and P.R.

Grant. 1988. Natural
Selec+on in a popula+on
of Darwins Finches. Am
Nat. 133, 377-393.

Processes thought to
have driven
specia+on of
Galapagos nches
are s+ll happening.

In this case
adap+ve (posi+ve)
selec+on for larger
body size

During a drought in 1976-78 on the island of Daphne Major in the Galapagos

Archipelago, the population size of finches (Geospiza fortis) decreased (Graph A) due
to the decline in seed supply (Graph B), during which time the size and hardness of
the seeds increased (Graph C), as a result of which the average size of finches
increased (Graph D), because larger birds can handle such seeds more efficiently.

Adapta+on to a glucose limited minimal media, evolu+on is indicated by

increase in popula+on tness, measured rela+ve to an ancestor.
Es+mated # benecial muta+ons in 2000 genera+ons ~10 - 20 xed in
each popula+on (of ~100 xed - majority are neutral).
Posi+ve selec+on for
mutants with a posi+ve
increase in tness (+).

Muta+ons causing no
increase in tness are

Muta+ons having a
deleterious eect on
tness are eliminated
( nega+ve selec+on 5 -)

Random mating means that mating generally occurs

without a correlation with a genotype in particular, or
phenotypic variation in general.!

Non Random mating: !

(1)If mating between relatives happens more frequently than
expected by chance, then the offspring are inbred.!
(2)Alternatively if less frequently than by chance, there is
(3) If individuals mate with phenotypically similar individuals,
there is positive assortative mating - inbreeding!
(4)Alternately if individuals mate with phenotypically unlike
partners, there is negative assortative mating (or disassortative
mating ). !

Self pollinating plants present the extreme case of

inbreeding. The loss of heterozygosity is easy to track.

p2 =0.25, 2pq=0.5, q2 = 0.25

Half of the
offspring of
heterozygotes are
homozygous, the
decreases by 1/2
each inbred

q2 = 0.375

q2 = 0.4375

The allele frequencies are the same, p = 0.5, but

a`er the rst genera+on the popula+on is not in

Large Popula+ons Subdivided

In a large population there is a small chance that changes in allele

frequencies will be affected by stochastic demographic effects,
some individuals die and others fail to breed for unknown reasons
or chance effects. !
In a small population, chance inbreeding among a small number
of closely related individuals in a subpopulation, may cause
random changes in allele frequency. The smaller the population,
the more likely individuals are related by descent due to
Chance effects in a small population combined with inevitable
inbreeding causes allele frequencies to drift towards 1.0 (fixation)
or 0.0 (elimination).!

Evolution in small populations: genetic drift - random

demographic effects and unavoidable inbreeding in small
populations !


!Genetic Drift The figure above indicates the divergence in

hypothetical populations that started with( 50%) A alleles and
(50%) a. Eventually one or the other allele goes to fixation in each
sub- population by chance. !


Random genetic drift . The graph on the left is a simulation of drift with 16 individuals, in 107
populations that are initially heterozygous. The messier graph on the right is a real - life experiment
with 16 individuals that were heterozygous for the bw/bw75 allele that shows the same pattern
expected for a small population that is drifting in allele frequency.
[Data in part (A) from P. Buri. 1956. Evolution 10: 367. Graphs from D. L. Hartl and A. G. Clark.
1989. Principles of Population Genetics. Sunderland, MA: Sinauer Associates]

genetic drift eliminates most but not all mutations, regardless

of their selection coefficients. The time to fixation depends on
chance, population size and selection. A longer time means a
greater chance of being lost!
The amount of +me for a
new advantageous
Most rare variants are lost by chance. The lower
the posi+ve selec+on coecient , the longer the
muta+on to increase in
+me to xa+on and the higher the chance of loss.
frequency to near xa+on is
inversely propor+onal to its
e.g. Large posi+ve
advantage (10%), small
number of genera+ons
Small advantage (0.1%),
large number of
genera+ons (25,000)

Popula'on Evolu'on: Diversica'on into Subspecies and Specia'on

Posi+ve selec+on, founder eects and

dri` make subpopula+ons diverge
whereas migra+on makes them more
Synthetic Neo-Darwinism admits
that founder effects, drift,
migration, although most
importantly positive selection
influence changes in allele
frequencies between
populations, which if large
enough can lead to speciation,
diversification of 1 ancestral
species. !

Represen'ng gene'c change at the species level -

phylogene'c trees
Phylogene+c trees:
(1)reconstruct genealogical trees-ancestor
descendent rela+ons
(2)Es+mate the +me of divergence between
taxa, since they last shared a common


Process underlying a gene tree

external nodes

internal nodes



Analogy would lead me one step further, namely, to the

belief that all animals and plants have descended from one
prototype( Darwin 1859).!
Recent gene trees tes+ng rRNA coding and other DNA sequence
coalescence indicates all organisms are monophyle'c. That is,
plants, animals, fungi and prokaryotes share a common ancestor.


Diversica+on and Phyle+c Evolu+on - a conceptual model


Gene+cs of reproduc+vely
independent lineages (e.g.
species) addresses lineage
ex+nc+on and ancestral
rela+onships represented as
phylogenies, here as a branching
In an environment that limits
their number, through selec+on
or by chance, some of the
chromosome or gene lineages
will go ex'nct and they will be
replaced, by other expanding,
diverging clades (ancestor and
its descendants).

The neutral theory of molecular evolution was developed to

(1) the unexpectedly high levels of molecular variation discussed
by Lewontin 1974 and !
(2) what looked to be the constancy through time of amino acid
Kimura (1968) argues that most molecular variation, substitutions
in homologous molecules between species and polymorphism or
mutation within them is due to neutral variation and genetic
drift. (M. Kimura. 1983. The Neutral Theory of Molecular Evolution.

Most eukaryo+c bases are not coding.

Molecules are muta+ng, some, possibly
most muta+ons have ligle eect on
func+on. Some will be xed by chance.
The rate of sequence evolu'on refers to
the frac+on of sites that change in a
period of +me (genera'on or calendar
'me). The muta'on rate per genera'on
is dened as (per gene per genera+on).
In any genera+on, in a diploid popula+on,
the expected number of new muta+ons
(per gene, per generation) is: 2N
2(chromosomes) *N (popula'on size)*


In any genera+on, in a diploid popula+on, the

expected number of new muta+ons is: 2*N * .

The probability that any one gene lineage will
replace the other by chance is 1/(2N).

Thus the expected number of new muta'ons or
sequence changes that are xed (in each
genera+on) is 2 N /2N =

a constant


The dierence in evolu+onary rates among molecules is

also a predic+on of Kimuras neutral model
Some molecules
evolve faster than
others, this
dierence in rate is
thought to indicate
dierences in
constraints (more or
less tolerant of
subs+tu+on or under
stronger stabilizing
selec'on) on the
whole gene, rather
than in a single
codon or exon. Note:
this is nega+ve or
elimina+on selec+on

Related sequences
(RNA pol II in L.
Reading the DNA
story ) show a
nested hierarchy
of substitutions
under strong
selection related to
divergence times:
Human- rat- 4bp
0 AA chg
Human- fly-9bp
0 AA chg
Fungus-11bp 1 AA
Human -plant-20bp
6 AA chg
Human-E coli-23bp
8 AA chg

Compara+ve gene+cs: sequence

varia+on for beta clamp protein


Molecular changes that are less likely to be subject to nega+ve

((elimina+ng, stabilizing ) selec+on, occur more rapidly in evolu+on.
Thus, Kimura argues in The neutral theory of molecular evolu+on that
most molecular change is neutral.
Viral protein


Nucleo+des in which posi+on (rst, second , third base in a codon) are evolving the
fastest ? Why ? func+onal constraints.
Between introns and exons, which might be the fastest evolving ?


Gene+c Varia+on
among Geographic

A major fraction of human

genetic variation is found in
small populations, or there is
little genetic evidence for races.
Both protein polymorphisms
and DNA markers concur that
85-95% of variation was within
groups, 7-10% of variation was
between continental groups!
This suggests that our species underwent a recent
expansion from a small popula'on.


Paleontologist generally agree that Homonids evolved in Africa un+l 1-2 million years ago.
There are two main theories about subsequent evolu+on of Homo sapiens:

Multiregional model: The traditional paleontological model has Homo erectus

migrating out of Africa 1-2 million years ago, colonizing Europe and Asia and
more or less simultaneously evolving into Homo sapiens, because of relatively
high migration and intermixing.!
Out of Africa model: after H. erectus had colonized Europe and Asia, modern
H. sapiens evolved in Africa, and began migrating to Europe and Asia,
50-100,000 years ago.!

Mitochondrial DNA is a single circular chromosome, that (almost) never



Within-species, mitochondrial and nonrecombining Y chromosome regions as

well as low recombination autosomal
haplotypes can be used to make a genetree. mt DNA evolves sequence changes at
a constant rate, about 1 change per
mitochondrial lineage per 4,000 years. The
observed number of dierences is used to
es+mate divergence +mes between
dierent popula+ons.
The fossil record (the oldest modern skull
unearthed @ 170, 000 yra) and Y
chromosome data (130-156 kya) are
consistent with the idea that we are a
young species, that recently migrated out
of Africa. There is at least 2X as much
variation in Africa than in the rest of the
world combined.

There is about twice as much mtDNA varia+on among Africans as

non-Africans, much mtDNA diversity is only found in Africa. The
diversity of tandem repeat varia+on on the le` is consistent with
this data. Both support the idea that modern human popula+ons
rst migrated out of Africa 100,000 years ago.


100,000 yr