Effective population size and patterns of molecular evolution and variation

Key Points

  • The effective size of a population, Ne, determines the rate of change in the composition of a population caused by genetic drift, which is the random sampling of genetic variants in a finite population. Ne is crucial in determining the level of variability in a population, and the effectiveness of selection relative to drift.

  • There are three major ways by which the rate of genetic drift can be modelled in the simplest type of population: increase in variance of allele frequencies; approach to identity by descent of all alleles; and coalescence of a sample of alleles into an ancestral allele.

  • A general method for calculating Ne has been developed using coalescent theory for populations in which there are several 'compartments' (for example, ages or sexes) in the population from which alleles can be sampled. This involves the fast timescale approximation, in which the flow of alleles between compartments is faster than the rate of coalescence.

  • Formulae are presented for the effects on Ne of differences in numbers of breeding males and females, differences in variance of offspring number between males and females, levels of inbreeding, changes in population size and modes of inheritance.

  • Methods for estimating Ne for natural and artificial populations are described, using both demographic and genetic approaches. Examples of the results of the application of these methods are presented.

  • The theory of how selection operates in a finite population is outlined, based on the formula for the probabilities of fixation of favourable and deleterious mutations. These depend on the product of the selection coefficient and Ne.

  • There are data that show that the level of molecular sequence adaptation is reduced when Ne is low, as predicted from the product of the selection coefficient and Ne.

  • The problem of describing neutral variability and the outcome of selection in a spatially or genetically structured population is discussed. A great simplification occurs when there is a large number of local populations in a structured metapopulation.

  • Selection at one or more sites in the genome can influence the value of Ne at other, genetically linked sites by several mechanisms. Balancing selection can elevate Ne, whereas positive selection and purifying selection reduce it.

  • Data on molecular variation and evolution are described, which are consistent with these theoretical predictions.

Abstract

The effective size of a population, Ne, determines the rate of change in the composition of a population caused by genetic drift, which is the random sampling of genetic variants in a finite population. Ne is crucial in determining the level of variability in a population, and the effectiveness of selection relative to drift. This article reviews the properties of Ne in a variety of different situations of biological interest, and the factors that influence it. In particular, the action of selection means that Ne varies across the genome, and advances in genomic techniques are giving new insights into how selection shapes Ne.

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Acknowledgements

B.C. thanks the Royal Society for support from 1997–2007.

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Glossary

Genetic drift

The process of evolutionary change involving the random sampling of genes from the parental generation to produce the offspring generation, causing the composition of the offspring and parental generations to differ.

Poisson distribution

This is the limiting case of the binomial distribution (see next page), valid when the probability of an event is very small. The mean and variance of the number of events are then equal.

Coalescent theory

A method of reconstructing the history of a sample of alleles from a population by tracing their genealogy back to their most recent common ancestral allele.

Coalescence

The convergence of a pair of alleles in a sample to a common ancestral allele, tracing them back in time.

Fast timescale approximation

Used to simplify calculations of effective population size, by assuming that the rate of coalescence is slower than the rate at which alleles switch between different compartments of a structured population as we trace them back in time.

Panmictic

A panmictic population lacks subdivision according to spatial location or genotype, so that all parental genotypes potentially contribute to the same pool of offspring.

Binomial distribution

Describes the probability of observing i independent events in a sample of size n, when the probability of an event is p. The mean and variance of the number of events are np and np(1 − p), respectively.

Neutral diversity

Variability arising from mutations that have no effect on fitness.

Heterogamety

The presence of two different sex-determining alleles or chromosomes in one of the two sexes.

Selection coefficient

(s). The effect of a mutation on fitness, relative to the fitness of wild-type individuals. With diploidy, this is measured on mutant homozygotes.

Metapopulation

A population consisting of a set of spatially separate local populations.

Semi-dominant or haploid selection

With a diploid species, semi-dominant selection occurs when the fitness of the heterozygote for a pair of alleles is intermediate between that of the two homozygotes; haploid selection applies to haploid species, and is twice as effective as semi-dominant selection with the same selection coefficient.

Dominance coefficient

(h). Measures the extent to which the fitness of a heterozygote carrier of a mutation is affected, relative to the effect of the mutation on homozygous carriers.

Heterozygote advantage

The situation in which the fitness of a heterozygote for a pair of alleles is greater than that of either homozygote. This maintains polymorphism.

Frequency-dependent selection

Situations in which the fitnesses of genotypes are affected by their frequencies in the population. Polymorphism is promoted when fitness declines with frequency.

Background selection

The process by which selection against deleterious mutations also eliminates neutral or weakly selected variants at closely linked sites in the genome.

Hill–Robertson effect

The effect of selection on variation at one location in the genome and on evolution at other, genetically linked sites.

Selective sweep

The process by which a new favourable mutation becomes fixed so quickly that variants that are closely linked to it, and that are present in the chromosome on which the mutation arose, also become fixed.

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Charlesworth, B. Effective population size and patterns of molecular evolution and variation. Nat Rev Genet 10, 195–205 (2009). https://doi.org/10.1038/nrg2526

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