Genetic drift Flashcards
What is genetic drift?
Natural Populations are finite in size
In finite populations there will be random changes in allele frequencies due especially to chance events, such as variation in the number of offspring between individuals.
This is Genetic Drift.
Modelling Genetic Drift
The fate of an allele is governed by chance, and this is most pronounced in small populations
Simulation based on the Wright- Fisher Model (assume neutrality):
each new generation is obtained from the previous generation by repeating the following 3 steps:
1) choose an allele at random from among the 2N alleles in the parent generation.
2) make an exact copy of the allele
3) place the copy in the new generation.
[for N=20 (40 allele), repeat 40 times]
Note: the key is that each of the 2N alleles has an equal chance of having a copy appear in the next generation. This model is a simplification that predicts the real situation well.
Wright Fisher Model interactive site modelling with flies:
https://virtualbiologylab.org/NetWebHTML_FilesJan2016/GeneticDriftModel.html
Implications of genetic drift
random changes in allele frequency - same start, different outcomes: evolution can never be repeated.
alleles are lost from the population, so genetic drift always removes variation from populations.
the direction of change is neutral.
Diversity of 0.5:
A population of 4 results in loss of diversity after 20 generations
A population of 40 results in loss of diversity after 80 generations (but some is still retained after 100 generations)
A population of 400 results in a 20% reduction in diversity after 100 generations
Decay of heterozygosity
Consider a simple model where there is just one hermaphroditic individual with the genotype Aa,
And the population size remains I.
Next generation the probability of being a heterozygote is 1/2 times the probability of being a heterozygote in the previous generation (because there ‘s half as many heterozygotes now)
In this simple model, probability of being a
heterozygote after t generations is (1/2)^t
General case for sexual diploids
Ht=H0 (1-1/2Ne)^t
or
Ht=Ht-1 (1-1/2Ne)
Effective Population Size (Ne)
Ne =The size of an ‘ideal population’ that would lose heterozygosity at the same rate as the real population.
A Wright-Fisher ideal population has constant size, random mating, discreet generations, sex ratio of 1, no migration, mutation or selection.
Another way to look at the loss of H in diploid, sexual species:
the chance that two identical alleles unite to form a zygote is:
1/ 2Ne
(^When they do, heterozygosity is lost).
The chance that they do not unite is:
1- (1/ 2Ne)
Ht+1 = (1- 1/ 2Ne) Ht
Example: An empirical study on Drosophila melanogaster (Buri 1956 Evolution 10:367-402)
- Established 107 Drosophila populations.
- All founders were heterozygotes for the eye-color gene ‘brown’ (genotype: bw75/bw).
- No dominance
- Initial frequency of bw75 = 0.5
- Followed the populations for 19 generations, and kept the population size at 16 individuals
- Data followed Ne and not Nc
- Observed that all began heterozygous and over generations became more homozygous resulting in peaks at each end due to each fly being homozygous – having 0 or 1 rather than the 0.5 at the beginning
What happens when a population is suddenly reduced in size?
This is a population bottleneck, and there are two consequences:
- first, a stochastic sampling of alleles
- second the loss of heterozygosity over time due to small population size.
drift occurs on a timescale of 2Ne generations
but the Hardy Weinberg equilibrium can be reached after 2 generations of random mating
Therefore, the Hardy Weinberg equilibrium will only be greatly affected by drift when Ne is very small – Hardy Weinberg remains valid in spite of drift in most cases
Mutation and Genetic Drift
If genetic drift is removing variation over time, why do natural populations retain variation?
MUTATION!!
u = the mutation rate = ~l x 10^-8 for mammals
Mutation introduces variation at a rate of 2Neu
(number of gametes recombining in a diploid
times the probability that one will include a
mutation)
Genetic drift gets rid of variation at a rate of 1/2Ne
Equilibrium is reached when the evolutionary
forces of drift (which eliminates variation) and
mutation (which adds variation), balance.
Since the average number of new mutations entering
the population each generation is 2Neu, and the
chance of fixation of the new mutation is 1/2Ne, the
average rate of substitution for Neutral mutations is:
2Neu X u
This means that for neutral mutations, the rate of
substitution depends only on the mutation rate, and
not on population size. Why? - because both drift
and mutation rate depend on population size in such a
way that this factor is cancelled out. This changes
when there is selection.
de novo variation introduced by mutation, is then
modified by subsequent forces of selection and drift.
Eventually, the measured rate will reflect new variants
shared by all members of the population (the
substitution rate), which can be more than an order of
magnitude lower than the de novo mutation rate.
See: Hoelzel & Lynch (2023) The raw material of
Evolution. Science 381, 942-943
As new mutations go to extinction or fixation over time,
there will be a lot of variation in natural populations that
reflects the transient representation of new alleles
(from Hoelzel & Dover 1991)
Neutral Theory of Evolution
proposes that most DNA variation is neutral, and that this is the basis for evolution
Kimura & Ohta (1971) Nature 229:467-469
“A population that is free from selection can accumulate many polymorphic neutral alleles. Then, if a change in ecological circumstances occurs, some of the neutral alleles will no longer be neutral but deleterious, against which purifying selection may operate. After these alleles are removed, the population will become more adapted to its new circumstances than before.”
Kimura (The Natural Theory of Molecular Evolution, 1983)
“I am inclined to suspect that we see, at least in some of these polymorphic genera, variations which are of no service or disservice to the species(neutral), and which consequently have not been seized on and rendered definite by natural selection.”
Charles Darwin (The Origin of Species)
Predictions
Previously we saw how sequence data from the ADH gene supports a prediction from neutral theory: that there should be high levels of variation in natural populations.
Another prediction is that change should accumulate gradually over time (provided that mutation is random, neutral, and selection acts primarily to purge deleterious variation).
Genetic drift explains the high level of variation we observe despite the fact that natural evolution drives species with purifying selection
DNA Sequencing improved accuracy
The advent Of DNA sequencing made the assessment of change over time more accurate, and provided the
opportunity to compare change at synonymous
(dashed line) vs non- synonymous sites
as seen in the example in notes: a study on the insulin gene (Li et al. 1985 in Molecular Evolutionary Genetics)
