Deleterious Variation in Natural Populations and Implications for Conservation Genetics

Abstract

Deleterious mutations decrease reproductive fitness and are ubiquitous in genomes. Given that many organisms face ongoing threats of extinction, there is interest in elucidating the impact of deleterious variation on extinction risk and optimizing management strategies accounting for such mutations. Quantifying deleterious variation and understanding the effects of population history on deleterious variation are complex endeavors because we do not know the strength of selection acting on each mutation. Further, the effect of demographic history on deleterious mutations depends on the strength of selection against the mutation and the degree of dominance. Here we clarify how deleterious variation can be quantified and studied in natural populations. We then discuss how different demographic factors, such as small population size, nonequilibrium population size changes, inbreeding, and gene flow, affect deleterious variation. Lastly, we provide guidance on studying deleterious variation in nonmodel populations of conservation concern.

Keywords: conservation biology; deleterious mutations; genetic load; inbreeding depression; simulations.

Figure 1

The distribution of fitness effects and the fate of mutations in populations. (a) Each new mutation that occurs in an individual has a selection coefficient (s) describing its effect on fitness. The distribution of values of s is called the distribution of fitness effects (DFE) and has been estimated for nonsynonymous mutations in several species. (b) Once a mutation enters the population, its fate is affected by natural selection and genetic drift. Natural selection will push beneficial alleles to higher frequency and deleterious alleles to lower frequency, whereas drift could allow for random fluctuations in allele frequency. (c) The distribution of selection coefficients for variants segregating in the population differs from the DFE of new mutations. The DFE for segregating variants (c) has been affected by selection and drift. Typically, the distribution of selection coefficients for segregating mutations will be shifted toward more neutral variants because the most deleterious mutations will have been eliminated by natural selection. The selection coefficients for the segregating variants are most directly relevant for assessing the genetic load of a population.

Figure 2

Genetic drift and inbreeding have different effects on the genome and on deleterious variation. (a, left) Genetic drift associated with a small population size leads to low heterozygosity across the genome. (right) Genetic drift also allows weakly deleterious mutations to become fixed in the population, contributing to drift load. The right-hand panel shows the probability of fixation for a new mutation with s specified by the different lines in a population of the size denoted on the x-axis. Probabilities were calculated using equation 10 in Reference . (b, left) Inbreeding can lead to a sawtooth pattern of heterozygosity across the genome. Regions of low heterozygosity correspond to the regions of the genome that likely are copies of the same ancestral chromosome inherited from both parents. (right) Inbreeding results in an increase in the probability of an ancestral chromosome (denoted by a) being inherited from both the maternal and paternal lineage, increasing homozygosity. Thus, recessive deleterious mutations have a higher probability of becoming homozygous and thereby affecting fitness.

Figure 3

Simulation workflow for genomic forecasting including genomic data and deleterious mutations. This framework was used to show that the vaquita is not doomed to extinction from inbreeding depression (83).