Download Population substructure

Population substructure
Most organisms do not occupy
a continuous range in time and
space
Toads and roads
• Panmictic
• A=a=p=q=0.5 initially
• What will happen to the frequency of A
and a, assuming that both alleles are
neutral and the toad population is finite?
Toads and roads
• Panmixia within each subpopulation
• A=a=p=q=0.5 initially in all subpopulations
• What will happen to the frequency of A
and a, assuming that both alleles are
neutral and each toad subpopulation is
finite?
Toads and roads
Subpopulations can diverge in allele frequencies
even if there is random mating within each
subpopulation. This population differentiation is
due to random genetic drift. The result of population
subdivision is reduced heterozygosity and
deviation from HWE among subpopulations.
Wright’s Fixation Index
(FST)
Sewall Wright
1889-1988
Hierarchical F statistics
I = individual
S = subpopulation
T = total population (assumed panmictic)
FIS can be thought of as:
• F
• Proportional loss of heterozygosity due
to recent common ancestry
FST can be thought of as:
• Proportional loss of heterozygosity due
to population subdivision and
subsequent random genetic drift
• Proportion of total genetic variance
found among populations rather than
within them
FIT can be thought of as:
• Proportional loss of heterozygosity due
to recent common ancestry and
population substructure
Hierarchical F statistics
HI = observed heterozygosity (usually
with molecular markers) averaged
among individuals within a
subpopulation
HS = expected (HWE) heterozygosity for
each subpopulation, averaged across
all subpopulations (2pq)
HT = expected (HWE) total heterozygosity
based on allele frequency and without
reference to any population
substructure (2pq)
FIS = (HS-HI)/HS
FST = (HT-HS)/HT
FIT = (HT-HI)/HT
AA: p2 + pqFST
Aa: 2pq – 2pqFST
aa: q2 + pqFST
Hierarchical F statistics
According to Sewall Wright:
FST ranges from 0-1
• 0 = no genetic differentiation; panmixia
• 0.00–0.05 = little genetic diff
• 0.05-0.15 = moderate genetic diff
• 0.15-0.25 = great genetic diff
• 0.25-1.00 = very great genetic diff
• 1 = complete genetic differentiation
Plant mating system
Selfing
Mixed (animal)
Mixed (wind)
Outcrossing (animal)
Outcrossing (wind)
From Hamrick and Godt (1989)
N
78
FST
0.510
60
0.216
11
124
134
0.100
0.197
0.099
Hierarchical F statistics
According to Sewall Wright:
FST ranges from 0-1
• 0 = no genetic differentiation; panmixia
• 0.00–0.05 = little genetic diff
• 0.05-0.15 = moderate genetic diff
• 0.15-0.25 = great genetic diff
• 0.25-1.00 = very great genetic diff
• 1 = complete genetic differentiation
Organism
Human ‘races’
Yanomamo villages
House mouse
Jumping rodent
Drosophila equinoxialis
Horseshoe crab
From Hartl & Clark, Principles of Population Genetics
FST
0.069
0.077
0.113
0.676
0.109
0.076
From Anne Chung
www.apamsa.org/files/APAMSA%20presentation-general.ppt
Percentage Slow Metabolizers
• Drugs metabolized by N-acetyltransferase
– Nydrazid (anti-TB)
– Sulfonamides (antibiotic)
– Procanbid (antiarrhythmic)
– Hydralzaine (antihypertensive)
– Caffeine
60%
50%
40%
60%
30%
20%
10%
0%
20%
Asian
Caucasian
Price Evans DA. N-acetyltransferase in pharmacogenetics of drug
metabolism. In Kalow W, ed. Pharmacogenetics
of drug metabolism. International encyclopedia of pharmacology and
therapeutics. New York: Pergamon Press,
1992: 43:95-178.
Racial differences in
human populations
• Why is this observation
interesting to evolutionary
biologists?
• Why is this observation
interesting to physicians and
drug companies?
• Why is this observation
interesting (and contentious) to
society?
• What evolutionary and nonevolutionary mechanisms could
explain this observation?
American Anthropological
Association (Am Anthropol 1998;
100: 712-713)
It has become clear that human
populations are not
unambiguous, clearly
demarcated, biologically distinct
groups. . . . Throughout history
whenever different groups have
come into contact, they have
interbred. The continued sharing
of genetic materials has
maintained humankind as a
single species. . . . Any attempt to
establish lines of division among
biological populations is both
arbitrary and subjective.
Does “race” have
biological meaning?
• Is shared skin color a good
surrogate for shared
ancestry?
• How could shared ancestry
in human populations be
determined?
How could shared ancestry in
human populations be determined?
• Is shared skin color a good surrogate for
shared ancestry?
• Can the genetic distance tree above be
reconciled with the statement from the AAA?
• Should human population structure be
considered during drug development/testing?
• What evolutionary and non-evolutionary
mechanisms could explain variation in drug
response among human populations?
Migration and FST
At equilibrium, FST = 1/(4Nm + 1)
What is Nm, in biological terms?
What effect does migration have
on population differentiation due
to genetic drift?