Download BioA414 Handout VII-2017

Mutation
BioA414
Population Genetics
Handout VI
Mutation
• Heritable changes within DNA
– Converts one allelic form of a gene to
another
– Rate  low and varies between loci and
between species
– Env. Factors  chemicals, radiation and
infectious agents  ↑number of mutations
• Source of all new genetic variation
• Raw material for evolution
Spontaneous mutation frequencies
at specific loci for various
organisms
• Probability  likelihood  an error will
occur + it will be repaired
– Synonymous mutation  no alteration of the
amino acid
– Nonsynonymous mutation  alteration of
the amino acid
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Spontaneous mutation frequencies at
specific loci for various organisms
Organism
Trait
Mutation/100,000
game tes
Consider a hypothetical
population
• p = f(A) and q = f(a)  assume large
population + no selection
• In each g.  a proportion u of all A a
– Number of mutati ons depends on u and p
A pop. of 100,000 A  u equals 10 -4 , 1/10,000 A  a
p = 1.0 10 -4 x 100,000 = 10
p = 0.1  10 -4 x 10,000 = 1
– The decrease in p due to A a = up
– The increase in p due to A a = vq
– Amount of A ↓ = increase in A (reverse mutations) –
decrease in A (forward mutations)
Mutation rate varies between loci
and among species
• ~10-4 to 10-8 mutations/gene/generation
• Mutation rate is abbreviated 
• Some mutations are neutral (no effect on
reproductive fitness)
• Others are detrimental or lethal (depends
on environment)
• If population size is large, effects of
mutation act slowly
Equilibrium frequencies
• Forward mutation rate ↑ q and a reverse
mutation rate ↓ q
• The population achieves equilibrium
– Nb of alleles undergoing forward mutation =
Nb of alleles undergoing reverse mutation
– At this point no change in allelic freq occur
– The equilibrium q = …
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Equilibrium frequencies
Equilibrium frequencies
• The equilibrium value of p = …
• A population  initial p = 0.9 and q = 0.1,
u =5x10-5 and v = 2x10-5
– Calculate the change in allelic freq in the
first generation
Irreversible mutation
Allele A is fixed (p =1.0)
and mutates A  a at
rate of  = 10 -4
Reversible mutation
Allele A is fixed (p =1.0) and
mutates A  a at rate of  = 10 -4 ;
but allele a mutates a  A at a
rate of  = 10 -5
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Effective population size
• Not all individuals contribute gametes to the
next generation
• Effective population size (Ne) = equivalent
number of adults contributing gametes to the
next generation
• Ne = (4 x Nf x Nm )/ (Nf + N m )
• If ♂=♀, Ne = N
Genetic drift
• Island population of 10 individuals  5
with brown eyes (BB) and 5 with green
eyes (bb); f(B) = 0.5, f(b) = 0.5
• Typhoon devastates the island  5
people with brown eyes (BB) die
• Allelic frequency of b, f(b) = 1.0
• Now imagine the same scenario for an
island of 10,000 inhabitants
Fixation of a new favorable
mutation
• May occur rapidly
• Selective sweep
• Tightly-linked neutral alleles 
hitchhiking during a selective sweep
• Linked regions of DNA around the
favorable allele are overrepresented in
the population  leads to excess of rare
alleles at linked loci
The fixation or loss of
alleles by random
genetic drift occurs
more rapidly in small
populations
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Sampling occurs naturally
The effect of genetic drift is inversely
related to population size
• Which gametes fertilizes the egg?
• What proportion of offspring survive?
• What proportion of offspring contribute
gametes to the next generation?
Large populations = small effe cts
A genetic
bottleneck
Small populations = large e ffe cts
A population bottleneck
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Population bottleneck followed by
recovery or extinction
Genetic Bottleneck
A historical case
A severe genetic bottleneck occurred in northern elephant seals
European bison/ wisent
(Bison bonasus)
American
bison/ American buffalo
(Bison bison)
Bison bison faced extinction
around the year 1890
Year
American bison
Before 1492
60,000,000
1890
750
2000
360,000
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The Island of the Colorblind
• Pingelap island in Micronesia  pop. has
an high (5%) freq. of achromatopsia
• Achromatopsia is a rare, autosomal
recessive  total inability to distinguish
colors
• A typhoon ↓ island’s population 
subsequent inbreeding increased the
recessive allele responsible for the disease
Tristan da Cunha
• A remote island in the south Atlantic
settled in 1817 by a Scotsman and his
family
• The current population can trace their
ancestry to about two dozen individuals
• Genetic structure reflects the distribution
of genes that happened to be present in
the small group of founders
Bottleneck and founder effects
• Sampling effects  occurs in natural
populations
– From founder effects  a populati on is established
by a s mall number of breedi ng indi vi duals
– Populati on size remains small / many generations
– Subpopul ations are isolated
– Chance pl ays a significant role in determining which
genes are present among the founders
The Founder Effect
One ancestor carrie d allele for retinitis pigmentosum
Among their 240 de scendents living on the island today, 4 are blind by the
disease and 9 othe rs are carrie rs
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The Dunkers
The Dunkers
• A religious isolate founded by about 50
families from Germany who settled in
Pennsylvania in 1719
• Allele freq.  ABO blood group, bent
little fingers, hitchhikers thumb  differ
• These differences  founder effect
The Founder Effect
Old Order Amish populations are deri ved
from a few dozen colonists
The community is closed
Allele and genetic disease frequencies are different from the
German ancestral and the surrounding l ocal popul ations
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Neutral theory of molecular evolution
Genetic drift
in Drosophila
•
Genetic drift cause s allele fre quencies to change ove r time
Some alleles may go extinct: p  0
–
Other alleles may become fixed: p  1
–
•
•
Probability of fixation increases with time
Which allele becomes fixed is strictly random
–
Rare alleles are more likely to be lost (p  0)
–
Time to fixation/loss varies with Ne and initial allele frequency
–
Neutral mutations can be used to estimate time elapsed since two
populations/species diverged from a common ancestor
Balance between mutation and
genetic drift
• Mutation adds genetic vari ation/genetic drift removes
vari ation
• Infinite alleles model predicts that mutation and dri ft
balance each other to result in a steady state of
heterozygosity
– Each mutation is assume d to gene rate a novel allele ne ve r
obse rve d
– Genetic drift ope rates as normal
– Hete rozygosity  H = (4 Ne )/ (1 + 4 Ne  )
– Neutral paramete r  = 4 Ne 
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