Mutation–Selection Balance

Abstract

An organism's genome is continually being altered by mutations, the vast majority of which are harmful to the organism or its descendants, because they reduce the bearer's viability or fertility. Consequently, in every generation, natural selection acts to weed out these deleterious mutations. The opposing processes of mutation and selection balance each other so that the frequency in a population of a deleterious mutation remains at an equilibrium value determined by the strength of selection and the frequency of mutation. The classic model of mutation–selection balance assumes a single biallelic locus under constant selection. In reality, selection and mutation can vary in time and space, loci can have multiple alleles, and the genome comprises many loci. Mutation–selection balance across the genome depends on factors such as linkage, recombination, mating system, epistasis, pleiotropy and the distribution of fitness effects of new mutations. Mutation–selection dynamics also inform genetic variance for quantitative traits under stabilising selection. Key Concepts: A deleterious mutation at a single locus has an expected equilibrium frequency determined by the rate at which it is produced by mutation, and the rate at which selection removes it from the population. The decrease in population fitness due to the accumulation of deleterious mutations under mutation–selection balance is called mutational load. In finite populations, deleterious mutations can depart from their equilibrium frequency, be lost or go to fixation, all by stochastic drift. Equilibrium expectations under the neutral model of mutation–selection balance provide important null hypotheses for measuring selection in natural populations. Mutation–selection dynamics at multiple loci depend on many factors such as dominance, recombination rate, linkage, epistasis, pleiotropy, mating system and population size. Variation at quantitative genetic traits can also be maintained by a balance between stabilizing selection and mutation.

Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV

“…In infinitely large populations, deleterious mutations are present at a constant frequency equal to u / s , where u is the mutation rate from wild-type to the mutant and s is the selection coefficient that reflects the negative fitness effect, or cost, of the mutation [ 13 , 14 ]. In natural populations of finite size, however, the frequency of mutations is not constant; instead it fluctuates around the expected frequency of u / s , because of the stochastic nature of mutation and drift [ 13 ].…”

Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula

“…In addition to identifying genetic loci associated with traits, GWAS can be used to estimate allele frequencies of associated SNPs and their effect size, which may reveal the forces of selection that contributed to the genetic architecture of a trait (Stinchcombe and Hoekstra, 2007;Josephs et al, 2017). In GWAS data, we expect that mutations (SNPs) with larger effect sizes will most often be deleterious (Eyre-Walker and Keightley, 2007) and be subject to purifying or negative selection (Trotter, 2014) under mutation-selection balance (Crow and Kimura, 2010). These processes can be revealed by negative correlations between SNP effect size (estimated in the GWAS) and minor allele frequencies (MAFs), where SNPs with smaller effect on a trait will be at higher frequency and those with a larger effect will be at lower frequencies (Stanton-Geddes et al, 2013;Josephs et al, 2015).…”