Download Gene Flow Gene Flow Between Two Demes

Gene Flow
• The Hardy-Weinberg Model Considered Only A
Single Population
• Most Species Have Many Local Populations
• Although Most Matings Usually Occur Within A
Local Population, Sometimes Individuals Mate
Outside Their Local Deme
• Reproductive Connections Between Demes Allow
Genes To Move From One Local Gene Pool To
Another.
• The Movement of Genes Between Demes
Is Called Gene Flow.
Gene Flow Between Two Demes
Local Population 1
Gene Pools At
Generation 0
A
p1
1-m
Gene Pools At
Generation 1
A
p1 ’
Local Population 2
a
q1
m
a
q1 ’
A
p2
m
a
q2
1-m
A
p2 ’
a
q2 ’
1
Gene Flow Between Two Demes
Local Population 1
Gene Pools At
Generation 0
A
p1
1-m
Gene Pools At
Generation 1
A
p1 ’
Local Population 2
a
q1
m
a
q1 ’
p1’ = (1-m)p1 + mp2
= p1 - m(p1-p2 )
A
p2
m
a
q2
1-m
A
p2 ’
a
q2 ’
p2’ = (1-m)p2 + mp1
= p2 + m(p1-p2)
Gene Flow Between Two Demes
p1’ = p1 - m(p1-p2)
p2’ = p2 + m(p1-p2)
Let do = (p1-p2) = the difference in allele frequencies
between the demes at generation 0.
Then:
p1’ = p1 -mdo
p2’ = p2 + mdo
Gene Flow (m > 0) Will Be An
Evolutionary Force When do≠ 0
That is, When The Initial Gene
Pools Are Different (p1 ≠ p2).
2
Gene Flow Between Two Demes
•m is defined in terms of the gene pools, and therefore m represents
the amount of exchange of gametes between the local populations and
not necessarily individuals.
•In some species, gametes are exchanged directly without the diploid
individuals moving at all. For example, most trees are wind
pollinated
•Because gene flow requires both movement and reproduction, m
represents a complex interaction between the pattern of dispersal and
the system of mating.
•In general, disassortative mating enhances gene flow (recall
Yanomama & Makiritare) and inbreeding & assortative mating
reduce gene flow for a given amount of dispersal of individuals.
Gene Flow Between Two Demes
The impact of system of mating on patterns and
amount of gene flow is illustrated by the admixture
of Europeans and Africans in the Americas.
3
Gene Flow Between Two Demes
West African Population
European Population
Ancestral
Gene Pools
A
a
A
a
pE
qE
pW
qW
M
1
Gene Pools in
Present North
America
1-M
A
a
A
a
pE
qE
p A = MpE+(1-M)pW
qA
European Americans
African Americans
Where M is the effective amount of gene flow since admixture
began (in contrast to m, a per generation gene flow parameter)
Gene Flow Between Two Demes
M=
!
pA " pW
Change in Allele Freq. in African Americans from West Africans
=
pE " pW Initial Diff. in Allele Freq. Between Europeans and West Africans
For Example, The Frequencies of the Rh+ Allele at
the Rh Blood Group Locus Are:
Western Europeans: 0.0279
Western Africans:
0.5512
African-Americans: 0.4381
So, M = (0.4381-0.5512)/(0.0279-0.5512)=0.216.
4
Gene Flow Between Two Demes
In Northeastern Brazil, there were many categories
for individuals of mixed ancestry, and because of
these social definitions, there was much more gene
flow between both parental populations.
Gene Flow Between Two Demes
E.g., self-identified “whites” in NE Brazil:
67% European
20%
African
13%
Native
American
E.g., self-identified “non-whites” in NE Brazil:
58% European
25%
African
17%
Native
American
5
The Evolutionary Impacts of
Gene Flow
Gene Flow Between Two Demes
Local Population 1
Gene Pools At
Generation 0
Gene Pools At
Generation 1
A
p1
a
q1
1-m
m
A
a
q1 ’
p1’= p1 - mdo
1-m
Gene Pools At
Generation 2
A
p1”= p1’-md1
m
a
q1 ”
Local Population 2
A
p2
m
a
q2
1-m
A p2’=
p2+ mdo
m
a
q2 ’
1-m
A p2”=
p2’+ md1
a
q2 ”
6
Gene Flow Between Two Demes
After 1 Generation of Gene Flow:
p1’ = p1 -mdo
p2’ = p2 + mdo
d1 = p1 ’ - p2 ’ = p1 -mdo - p2 - mdo
= p1 - p2 -2mdo
= do - 2mdo
= do(1-2m)
Can show that after n generations of gene flow:
dn = do (1-2m)n → 0 as n → ∞
Gene Flow Is An Evolutionary Force That
Reduces Genetic Differences Among Local
Demes
Gene Flow Between Two Demes
Gene Flow Is An Evolutionary Force That
Reduces Genetic Differences Among Local
Demes
For Example, The Frequenies of the Rh+
Allele at the Rh Blood Group Locus Are:
Western Europeans: 0.0279
Western Africans:
0.5512
African-Americans: 0.4381
7
Recall That Genetic Drift Increases Genetic Variation Between Demes
2N = 20
4 Isolated Demes Started
From One Ancestral
Deme With p = 0.5
p
Generation
Gene Flow Between Two Demes
Gene Pools At
Generation 0
Local Population 1
Local Population 2
A
p1 = 1
a
q2 = 1
1-m
Gene Pools At
Generation 1
m
A
a
p1’ =1-m q1’=m
m
1-m
A
p2’=m
a
q2’=1-m
Gene Flow Is An Evolutionary Force That Increases
Genetic Variation Within Local Populations
8
Recall That Genetic Drift Decreases Genetic Variation Within Demes
Gene Flow And Genetic Drift
Have Opposite Effects on Genetic
Variation Within and Between Demes.
The Balance Between These Two
Evolutionary Forces Is The Major
Determinant of the Relative Amounts
of Genetic Variation Within Versus
Between Local Populations of A
Species.
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GLOBAL GENETIC DRIFT
MUTATION
ALLELIC DIVERSITY
NATURAL SELECTION
BALANCE BETWEEN
LOCAL GENETIC DRIFT
AND GENE FLOW
WITHIN LOCAL POPULATION
VARIATION
AMONG LOCAL
POPULATION VARIATION
RECOMBINATION
SYSTEM OF
MATING
HOMOZYGOTES
HETEROZYGOTES
MULTI-LOCUS COMPLEXES
Measuring the Balance of Gene
Flow and Genetic Drift
Sewall Wright
10
Wright Quantified The Balance of Gene Flow To
Drift as Measured by Fst for the Island Model
Common Gene Pool From All Local Demes
m
m
N
m
m
m
N
m
m
N
m
m
N
m
N
Local Demes
Impact of Drift and Gene Flow On
Average F In The Island Model
Effect of Drift Alone On The
Prob. Two Randomly
Chosen Genes are I.B.D:
F(t) =
(
)
1
+ 1 - 1 F(t-1)
2N
2N
With Gene Flow, Two Genes Can Only Be I.B.D. If They Are From the Same
Deme (by assumption), So:
F(t) =[
1
2N
+ (1 - 1
2N
)F(t-1)](1-m)
2
At equilibrium, F(t) = F(t-1) = F, and the above equation yields:
F = Fst ≈
1
4Nm+1
11
Impact of Drift and Gene Flow On
Average F In The Island Model
Fst ≈
1
4Nm+1
•Fst does not measure ibd in the usual pedigree sense,
but rather the ratio of drift to gene flow at the
population (mulitple deme) level
•This is yet another “inbreeding coefficient”, but this
one measures the proportion of genetic variation
among individuals drawn from all demes that is due to
genetic differences between demes.
Impact of Drift and Gene Flow On
Average F In The Island Model
•In many cases cannot distinguish ibd from identity by state.
•Let Fs be the probability of identity by state of two genes drawn
from within a subpopulation (local deme)
•Let Ft be the probability of identity by state of two genes drawn
from the total population.
•Now, Fst is additional probability of identity-by-state within a
deme that occurs because of between deme differentiation:
Fs = Ft + (1" Ft )Fst
Fst =
Fs " Ft
1" Ft
!
12
Gene Flow and Genetic Drift:
Fst ≈
1
4Nm+1
Region 1
…
…
Coalescence
Before Gene
Flow of Two
Randomly
Sampled Genes
From Region 1
…
An effective 1 migrant per generation (Nefm)
will keep Fst low for neutral loci.
Region 2
13
…
…
…
Gene Flow
Before
Coalescence of
Two Randomly
Sampled Genes
From Region 1
Region 1
Region 2
Gene Flow and Coalescence:
Prob.(gene flow before coalesence | gene flow or coalescence) "
4N ef m
4N ef m + 1
= 1 - Fst
!
Also, Slatkin (1991) showed:
4N ef m
t0
=
t 1+ 4N ef m
where t0 is the average time to coalescence of two genes sampled
from the same subpopulation and t is the average time to
!
coalescence of two genes sampled from the entire species.
!
!
14
The Wahlund Effect
Named after the person who showed that population
stratification can cause deviations from HardyWeinberg Genotype Frequencies.
This provides yet another measure of the ratio of
genetic drift to gene flow in terms of variances of allele
frequencies (not identities by descent or state) that is
called “fst”, which is often confused with Fst.
The Wahlund Effect
Let pi be the frequency of allele A in deme i.
Let N be the total population size (N=∑Ni).
Let wi the proportion of the total population that is in deme i (wi=Ni/N).
Assume (for now) random mating within each deme.
Then within deme i:
Genotype:
Frequency:
AA
pi2
Aa aa
2piqi qi2
15
The Wahlund Effect
For the total population:
n
Freq.(AA) = " wi pi2
i =1
n
Freq.(Aa) = 2" wi pi qi
i =1
n
Freq.(aa) = " wi qi2
i =1
!
The Wahlund Effect
By definition, the variance in allele frequency across demes is:
n
n
n
Var( p) = " p2 = $ wi ( pi # p )2 = $ wi p 2i # p 2 = $ wi q2i # q 2
i =1
So:
i =1
i =1
n
Freq.(AA) = " wi pi2 # p 2 + p 2 = p 2 + $ p2
i =1
!
n
Freq.(aa) = " wi qi2 # q 2 + q 2 = q 2 + $ p2
i =1
Freq.(Aa) = 1# Freq.(AA)# Freq.(aa) = 2pq # 2$ p2
(
Freq.(Aa) = 2 pq 1"
# 2p
pq
) = 2 pq (1" f )
st
fst = " p2 /( pq )
!
!
!
16
The Wahlund Effect
The Genotype Frequencies in the Total Population Are:
2
st
Freq.(AA) = p + pq f
Freq.(Aa) = 2pq(1" fst )
Freq.(aa) = q 2 + pq fst
fst measures the deviation from Hardy-Weinberg Genotype
Frequencies in the total population due to differences among demes.
Specifically, looks at deviations from expected heterozygosities:
!
fst = 1"
Freq.(Aa) 2pq " Freq.(Aa) H t " H s
=
=
2pq
2pq
Ht
!
The Average “Heterozygosity” Expected by Randomly Choosing Two Genes
From Within a Subpopulation = HS = [140(0.36)+372(0.29)]/512 = 0.309
H.-W. Het
= 2pq = .36
H.-W. Het.
= 2pq = .29
140 Pueblo Indians
M
N
0.76
0.24
372 Australian Aborigines
M
N
0.176
0.824
Total Population
M
N
[140(.76)+372(.176)]/512 =0.34
[140(0.24)+372(.824)]/512=0.66
The “Heterozygosity” Expected by Randomly Choosing Two Genes From
The Total Population = HT = 2pq = 2(.34)(.66) = 0.449
fST = (HT - HS)/HT = (.449-.309)/.449 = 0.312
17
fST Measures The Balance of
Gene Flow to Drift on a 0-1 Scale
HT = HS⇒
All Demes Have
Identical Gene Pools;
All Variation Shared
Equally Throughout
The Species
HS = 0 ⇒
No Variation Within
Demes; All Variation
Exists As Differences
Between Demes’
Gene Pools
0
1
fST = (HT-HS)/HT
Gene Flow dominates
Genetic Drift dominates
Human Population Structure
The Low fST Value For Humans Indicates Much
Gene Flow Among Human Populations
I C
E L
AND
MAD A
GAS
CAR
Between
continents
18
1
4Nm+1
F≈
Is defined in terms of identity by descent, so N is really Nef .
But fst is defined as deviation from HW, and Li (1955) showed
that the equilibrium variance under the island model is:
"2 =
fst " # p2 /( pq )
!
!
pq
2N ev # ( 2N ev # 1)(1# m)2
fst =
1
1
#
2N ev " ( 2N ev " 1)(1" m)2 4 N ev m +1
!
The Wahlund Effect and System of Mating
Let pi be the frequency of allele A in deme i.
Let N be the total population size (N=∑Ni).
Let wi the proportion of the total population that is in deme i (wi=Ni/N).
Assume non-random mating within each deme with fis.
Then within deme j:
Freq.(AA in deme j) = pj2 + pj qj fis
Freq.(Aa in deme j) = 2pj qj (1" fis)
Freq.(aa in deme j) = qj2 + pj qj fis
!
19
The Wahlund Effect and System of Mating
With respect to the total population, the AA genotype frequency is now:
n
Freq.(AA) = " wj ( pj2 + pj qj fis)
j =1
n
n
= " wj p + " wj ( pj # pj2 ) fis
2
j
j =1
j =1
= p 2 + $ p2 + fis( p # p 2 # $ p2 )
= p 2 + pq( fst + fis [1# fst ])
Let fit = fst +fis(1-fst)
Freq.(AA) = p 2 + pq f it
!
!
The Wahlund Effect and System of Mating
With respect to the total population, the genotype frequencies are:
Freq.(AA) = p 2 + pq fit
Freq.(Aa) = 2pq(1" fit )
Freq.(aa) = q 2 + pq fit
!
(1-fit ) = 1- fst -fis(1-fs) = (1-fst)(1-fis), so the deviation of
heterozygote genotype frequency from Hardy-Weinberg at the
total population level (1-fit ) is partitioned into a component
due to the local system of mating (1-fis) and a component due
to differences in allele frequencies across local demes (1-fst)
20
The Wahlund Effect and System of Mating
E.g., Yanomama:
fis = -0.01, indicating an avoidance of system–of–mating
inbreeding (incest taboo) and a slight excess of observed
heterozygosity within villages
fst = 0.073 (between villages)
fit = fst+fis(1–fst) = 0.073-0.01(0.927) = 0.064
Even though the Yanomama avoid inbreeding within villages
(fis = -0.01 < 0), the Wahlund effect creates an overall
heterozygosity deficiency (fit = 0.064 > 0) at the tribal level.
F/f ≈
The equation:
1
is NOT the universal relationship
4Nm+1
Between gene flow and genetic drift, as often presented. E.g., consider
the one-dimensional stepping stone model (isolation by distance):
Common Gene Pool From All Demes
m
m
m
m
m1/2
N
m
m 1/2
N
m 1/2
m
m
m1/2
N
m1/2
m
m
m 1/2
N
m 1/2
m
N
m1/2
21
Impact of Drift and Gene Flow On fst In
The Stepping Stone Model
fst ≈
1
1+ 4Nev√2m1m∞
When m1 >> m∞
Because the two migration parameters appear as the product
m1 m∞, this means that even small amounts of long distance
Gene flow have a major impact on fst.
The reason is that the evolutionary impact of gene flow
Depends both on the amount of gene flow and the difference
In allele frequency. The farther the distance, the greater the
Difference in allele frequency in general, so long distance
Dispersal has a disproportionate evolutionary impact.
Impact of Drift and Gene Flow On fst In
The Stepping Stone Model
fst ≈
1
1+ 4Nev√2m1m∞
When m1 >> m∞
E.g., let Nev = 100 and m1 = 0.1. Then
fst = 0.053 if m∞ = 0.01
fst = 0.276 if m∞ = 0.001
Note in this example that large differences in fst are invoked by
changes in long–distance dispersal even though long-distance
dispersal is ten to a hundred times less common than shortdistance dispersal.
22
Isolation By Distance in Continuously
Distributed Populations
• Let δ = the density of the individuals, (actually a variance
effective density)
•Let σ, the standard deviation of the geographical distance between
birthplace of parent and offspring
•There are no longer discrete demes, so use the concept of
Neighborhood Size (Wright, 1946) (the number of individuals
surrounding a point in space from which the parents of individuals
born near that point may be treated as if drawn at random):
Neighborhood Size for 1 dimension = 2"# $
Neighborhood Size for 2 dimensions = 4 $#" 2
!
Isolation By Distance in Continuously
Distributed Populations
•Retain m∞ as the long–distance dispersal parameter that measures
random dispersal over the entire species range.
•Then, at equilibrium, the fst among neighborhoods is:
fst "
!
1
1+ 4#$ 2m%
fst "
1
8#$% 2
1+
& ln( 2m')
For 1 dimensional habitats
For 2 dimensional habitats
!
23
Isolation By Distance in Continuously
Distributed Populations
Malecot showed that a general model of
isolation by distance yields:
fst(x)
fst(x) = ae-bxx-c where fst(x) is the pairwise fst between
Two populations separated by a distance x, where a & b are parameters
estimated from the data and c = 1/2(dimensionality of the habitat -1).
Humans at global level
24
Genetic Distance
• The pairwise fst is a type of population genetic
distance that quantifies the differences between
the gene pools of two populations
• Many other population genetic distances are
available, but all measure the degree of difference
between two gene pools
• Another type of genetic distance is a molecule
genetic distance that measures the difference
between two molecules of DNA; e.g., the
number or percent of nucleotide differences
fst and Molecule Genetic Distance
• When you survey for genetic variation at the DNA
sequence level, there is often so much variation that the
probability of two randomly chosen genes being identical,
even within the same deme, is very small and therefore
hard to estimate reliably. “Heterozygosity” within demes
often approaches one even when the demes’ gene pools are
very different, allowing little discrimination with fst .
• Instead of saying two genes are identical versus not
identical, we can use a molecule genetic distance to
measure the degree of non-identity
• Then you can perform a standard fst analysis using not
identity/non-identity, but rather a quantitative measure of
identity and non-identity. Such an analysis is called
AMOVA (Analysis of MOlecular VAriation)
25
Genetic Survey of Lipoprotein Lipase
LPL Has 10 Exons Over 30 kb of DNA on Chromosome 8p22
Sequenced 9,734 bp from the 3’ End of Intron 3 to the 5’ End of Intron 9
Sequenced:
24 Individuals from North Karelia, Finland (World’s Highest Frequency of CAD)
23 European-Americans from Rochester, Minnesota
24 African-Americans from Jackson, Mississippi
Found 88 Variable Sites
Ignored Singleton and Doubleton Sites and Variation Due to a Tetranucleotide Repeat, but
Phased the Remaining 69 Polymorphic Sites by a Combination of Using Allele Specific
Primer Pairs and “Haplotype Subtraction”
The Phased Site Data Identified 88 Distinct Haplotypes, treated as alleles; ie., 71
individuals with 88 alleles, with no allele being very common.
Genetic Survey of Lipoprotein Lipase
With 88 alleles in 71 individuals, with no allele being very common, almost every individual
was a heterozygote in all three populations. Hence, Hs, Ht ≈ 1, so fst = 0.02, not significantly
different from 0. Therefore, found no significant evidence for genetic differentiation among
these three populations
Instead of using heterozygosity, now use Φ = the Molecule Genetic Distance of the
number of nucleotides by which the pair of genes differed instead of identical vs. nonidentical.
Obtain Φst =
(Φt - Φs)/ Φt = 0.07, a value significantly different from zero.
Therefore, these populations did indeed show significant genetic differentiation, but these
differences were not detected by the traditional fst using haplotypes as alleles and
heterozygosity as a qualitative measure of genetic differentiation.
In general, when high levels of genetic variation are encountered, a quantitative scale of
differences between alleles is preferable to a qualitative one.
Like fst, Φst can be broken down into hierarchical components.
26
Multiple modes of inheritance
and population structure
• Recall that there are strong interactions between drift
and mode of inheritance (e.g., coalescent time):
Mitochondrial DNA
Y-Chromosomal DNA
2Nef♀=Nef (if Nef♀=1/2Nef)
2Nef♂=Nef (if Nef ♂=1/2Nef)
X-Linked DNA
3Nef
Autosomal DNA
4Nef
Multiple modes of inheritance
and population structure
• This also means that there will be strong interactions between
mode of inheritance and the ratio of drift to gene flow that
influences the degree of population subdivision. For example,
assume a species with a 50:50 sex ratio in which Nevm=Nevf=
Nev/2. Then, under the Island Model:
1
• For mtDNA
f st =
1+ N ev m
• For Y-DNA
f st =
1
1+ N ev m
!
• For X-linked DNA
!
• For Autosomal DNA
fst =
1
1+ 3N ev m
f st =
1
1+ 4N ev m
!
!
27
Gene Flow in Drosophila
mercatorum in Hawaii
28
Gene Flow in Drosophila
mercatorum in Hawaii
Autosomal genes,
fst=0.0002⇒Nevm > 2
Mitochondrial DNA,
fst=0.17⇒Nevm ≈ 5
Y-linked rDNA,
fst=0.08⇒Nevm ≈ 12
Using all the data,
Nevm is around 5-12
Gene Flow in Drosophila
mercatorum in Hawaii
fst =
1
1+ N ev m implies that both
PROBLEM: The equation
mtDNA and Y-DNA should yield the same fst and estimated
of Nevm, but fst(mtDNA) ≈ 2fst(Y-DNA).
!
The equality depends upon the assumption of a 50:50 sexratio (which is true in this case), equal reproductive
characteristics of both sexes (Nevm=Nevf), and equal m’s in
both sexes.
29
Gene Flow in Drosophila
mercatorum in Hawaii
Equal reproductive characteristics of both sexes. In most nonmonogamous species, the variance in offspring number is greater
in males than in females.
N ev =
2N
1" f 0 + vk (1+ f 0 )
Since we expect v in males > v in females, expect Nev(males) <
Nev(females) and fst(mtDNA) < 2fst(Y-DNA), exactly the
! the observation.
opposite of
Gene Flow in Drosophila
mercatorum in Hawaii
Equal m’s in both sexes. Mark-recapture studies show no
difference in dispersal probabilities or distributions in males and
females.
However, females store sperm and typically field caught females
have sperm from more than one male. Therefore, when a male
disperses, only male gametes are potentially being dispersed.
However, dispersing females disperse both female and male
gametes. So, even with equal dispersal rates for males and
females, there is actually much more gene flow of male gametes
than female gametes, so m(male)>m(female), which explains
the observations.
THINK LIKE A GAMETE!
30
Inbreeding Effective Size for the Island Model
with an Infinite Number of Demes
Common Gene Pool From All Local Demes
m
m
N
m
m
N
m
N
m
m
N
m
N
Local Demes What is the inbreeding
…
Let each local
deme be “ideal”
"µ + m%
N efT = N $
'
# µ &
m
…
m
effective size of the total
(infinite) population?
When m=0 (isolation), NefT =N, the local deme size.
With m>0, NefT increases with increasing m.
E.g., µ = 10-5 and m = 0.01, then NefT =1001N
!
Common Gene Pool From All Local Demes
m
N
m
m
N
m
m
m
N
m
N
m
m
N
…
m
Local Demes
31
…
Consider a finite island model of n local populations, each of ideal
size N, with a gene flow rate of m. The total population size in this
model is nN, and if the population were panmictic, its variance
effective size would be nN. Wright (1943) showed:
Note, as m→1, fst→0, and NevT→nN
nN
N evT =
1" fst
As m decreases, fst increases, and NevT >nN
Common Gene Pool From All Local Demes
!
m
m
N
m
m
N
m
m
m
N
m
N
m
m
N
Local Demes
Population Subdivision (decreasing gene flow) Decreases the
Total Inbreeding Effective Size, With The Limit Under Total
Isolation Being the Local Deme Size
Population Subdivision (decreasing gene flow) Increases the
Total Variance Effective Size, With the Limit Under Total
Isolation Being Infinity.
32
Warning!
• Although fst/Fst can be interpreted in terms
of the balance of gene flow and drift, it is
only a description of the current spatial
pattern of variation.
• E.g., suppose a population is split into two
isolated fragments with m = 0. At
equilibrium, fst = 1, but this can take many
generations to occur.
33