Genetic Drift

H-W model

constancy of allele proportions from one generation to next.

Populations are not infinitely large, their sizes are not constant, so

fluctuations in allele frequency can occur by chance ( )

genetic drift

Systematic evolutionary forces can also change allele frequencies. What are those forces?

• Mutation

• Migration

• Selection

In real finite sized populations may result in changes to allele

proportions due to:

-segregation of alleles (Mendel’s First Law)

-variation in the no. of offspring between individuals

chance fluctuations in allele frequencies occur, particularly in

small populations, as a result of

random sampling of gametes

because small samples are frequently not representative, an

allelic frequency in the sample may

differ from that in the entire

pool of gametes

If # gametes in sample is 2N (where N = no. of individuals) the

probability that the sample contains exactly 0, 1, 2, 3....2N alleles of

type A is given by

successive terms of the expansion (pA + qa)2N where

p and q are the allele frequencies of A and a in the parental generation

and p + q = 1

Probability sample contains exactly i alleles of type A is

[(2N)!/i!(2N-i)!] piq2N-i (binomial probability)

genetic drift causes

random changes in allele frequencies. alleles are lost from the population

the direction of random changes is neutral:

no systematic tendency

for the frequency of alleles to move up or down

Genetic drift is a===== process

random

the outcome of genetic drift cannot

be stated with certainty

genetic drift removes

genetic variation

The

probability that an individual chosen at random from the

population is heterozygous after t generations of random mating is

where H0 is the initial probability of being a heterozygote

and N is the population size

The probability of fixation of an allele, say A, (i.e. pA = 1) is equal to

the frequency of the A allele in the starting population

Genetic Drift

Genetic drift affects evolution in two ways:

• the dispersive force removes genetic variation from

populations (removal is inversely proportional to the

population size, so genetic drift is a very weak dispersive

force in most natural populations).

• drift’s effect on the probability of survival of new mutations,

an effect that is important even in the largest of populations.

• probability of fixation of an allele (i.e. pA = 1) is equal to

the frequency of the A allele in the starting population

The dispersive aspect of genetic drift is countered by

mutation, which

puts variation back into populations. These two forces reach an

equilibrium and can account for much of observed molecular variation.

Mutation provides

he raw material for evolutionary change but by

itself is a very weak force for changing allele frequency (in SNPs)

The mutation must be

non deleterious otherwise selection will

remove it from the population

Neutral Theory (1968 Kimura):

most polymorphisms observed at the

molecular level are selectively neutral. They produce such small

effects on ability of organism to survive and reproduce that they are

completely equivalent in terms of natural selection. (Their fate is

determined by genetic drift)

Mutation followed by genetic drift produces the variants

observed in

STRs

Mutation rates are high in STRs

(~10-3 per locus per

generation compared to SNPs (2.5 x 10-8 per base per

generation)

High mutation rate in STRs are why they are

highly polymorphic

STR mutational mechanism:

called DNA slippage, polymerase slippage, or slipped

strand mispairing (Kornberg 1964)

DNA slippage Looping out of

extending strand

+1

DNA slippage Looping out of

template strand

-1

Stepwise mutation model (SMM)

alleles can mutate up or down by one (or occasionally a small no. of

repeat units)

Factors Influencing STR Mutation

• No of Repeats: rate increases with repeat number

• Repeat unit size: dinucleotide repeats have higher mutation rate than

trinucleotide repeats

• Base composition of repeats: repeat units with a high AT content

mutate faster than those with a high GC content (template stability

affect?)

STR Mutations

Factors Influencing STR Mutation (con’d)

• Flanking sequence: if near hotspots of recombination,

mutation increases

• Sex: mutation of male gametes > female (more DNA

replication in males).

• Age: older males, more mitoses, more mutations than

younger males

• Interruptions in the STR repeats: more interruptions, lower

mutation rate

13

Migration, also known as gene flow, is

any movement of

individuals, and/or the genetic material they carry, from one

population to another (ie the movement of alleles from one

area (deme, population, region)

includes various events, such as pollen being blown to a

new destination or people moving to new cities or

countries

In a subdivided population random genetic drift results in

genetic divergence among subpopulations.

Migration

(movement of individuals among subpopulations) limits the

amount of genetic divergence that can occur.

If migrating individuals stay and mate with the

destination individuals,

they can provide a sudden influx

of alleles.

After mating is established between the migrating and

destination individuals, the migrating individuals will

contribute gametes carrying alleles that can alter the

existing proportion of alleles in the destination

population.

The genetic variation in modern human populations has

been critically shaped by

gene flow.

gene

flow introduced new genetic variation to the human

population through

interbreeding between ancient

humans and Neanderthals

Rates of migration typically much greater than

rates of

mutation, changes in allele frequency occur much

faster with migration

Natural selection

differential survival and

reproduction of

individuals due to

differences in phenotype