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					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                        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)
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                                                  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
From Anne Chung
www.apamsa.org/files/APAMSA%20presentation-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: 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 non-
  evolutionary 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?

				
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posted:5/12/2014
language:English
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