Perspective: Spontaneous Deleterious Mutation

Abstract

Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious‐mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long‐term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.

Genetic rescue guidelines with examples from Mexican wolves and Florida panthers

“…In the fruit fly, Drosophila melanogaster, approximately half the effect of inbreeding depression is thought to be from nearly recessive lethals and half from detrimentals of small effect but with higher dominance (Wang et al 1999;Lynch et al 1999). However, D. melanogaster generally has a very large effective population size ([10 6 ) and the genetic architecture of the detrimental genetic variation in this species probably reflects that of a large population near equilibrium.…”

Influence of the rate of introduction on the fitness of restored populations

“…New deleterious mutations stochastically occur in each diploid genome (Poisson distributed). Genetic parameters used for deleterious alleles (i.e., selective and dominance coefficients, and mutation rates) correspond to values commonly assumed for mildly deleterious and lethal mutations (Simmons and Crow 1977;Lande 1995;Drake et al 1998;Lynch et al 1999). However, due the lack of estimates of such parameters for adaptive mutations, we investigate broad ranges of values for the selective and dominance coefficients of these mutations.…”

“…On one hand, the reduction of viability and fecundity known as inbreeding depression is caused in part by the increasing homozygosity of numerous slightly detrimental mutations which may also become fixed despite counteracting selection, and accumulate (Morton et al 1956;Lande and Schemske 1985;Charlesworth and Charlesworth 1987;Lynch et al 1999). Another part of inbreeding depression is due to individually rare but collectively abundant, nearly recessive lethal or semi-lethal mutations (Simmons and Crow 1977;Lande 1988;Crow 1993;Wang et al 1998).…”

Genetic management of captive populations: the advantages of circular mating

“…Third, in our study, we assumed that genetic load is due to slightly deleterious partly recessive alleles with high mutations rates and to rare lethal alleles, according to several experimental observations and theoretical works (Lynch et al 1999;García-Dorado and Caballero 2000). However, for mildly deleterious alleles, the mean and distribution of their homozygous and heterozygous effect are currently under debate.…”

“…Fitness at locus i is 1, 1-h i s i , 1-s i for the AA, Aa, aa genotypes, respectively; where h i is the dominance coefficient and s i the deleterious effect of allele a in the homozygous state. We assumed that deleterious mutations fall into two classes: (i) slightly deleterious partly recessive alleles with dominance and selection coefficients h d = 0.3 and s d = 0.02, respectively, and (ii) highly recessive lethal mutations with h l = 0.02 and s l = 1, according to the literature (Crow 1993;Lynch et al 1999;. Although there is some controversy about the value of the genomic rate affecting fitness, is more likely that the genomic rate is rarely much less than 1 in multicellular organisms, and in certain taxa (e.g., primates) is probably greater than 1 (see Baer et al 2007 for further explanations and examples).…”