Population substructure

1
Population substructure

• Most organisms do not occupy a continuous range
  in time and space

2
Toads and roads

• Panmictic
• Aapq0.5 initially
• What will happen to the frequency of A and a,
  assuming that both alleles are neutral and the
  toad population is finite?

3
Toads and roads

• Panmixia within each subpopulation
• Aapq0.5 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?

4
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.
5
Wrights Fixation Index (FST)
Sewall Wright 1889-1988
6
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

7
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

8
Hierarchical F statistics

• According to Sewall Wright
• FST ranges from 0-1
• 0 no genetic differentiation panmixia
• 0.000.05 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 N FST
Selfing 78 0.510
Mixed (animal) 60 0.216
Mixed (wind) 11 0.100
Outcrossing (animal) 124 0.197
Outcrossing (wind) 134 0.099
From Hamrick and Godt (1989)
9
Hierarchical F statistics

• According to Sewall Wright
• FST ranges from 0-1
• 0 no genetic differentiation panmixia
• 0.000.05 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 FST
Human races 0.069
Yanomamo villages 0.077
House mouse 0.113
Jumping rodent 0.676
Drosophila equinoxialis 0.109
Horseshoe crab 0.076
From Hartl Clark, Principles of Population
Genetics
10
From Anne Chung www.apamsa.org/files/APAMSA20pres
entation-general.ppt

• Drugs metabolized by N-acetyltransferase
• Nydrazid (anti-TB)
• Sulfonamides (antibiotic)
• Procanbid (antiarrhythmic)
• Hydralzaine (antihypertensive)
• Caffeine

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
4395-178.
11
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 non-evolutionary mechanisms
  could explain this observation?

12
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.

13
Does race have biological meaning?

• Is shared skin color a good surrogate for shared
  ancestry?
• How could shared ancestry in human populations be
  determined?

14
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?

15
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?