New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster

Abstract

The genomic rate and distribution of effects of deleterious mutations are important parameters in evolutionary theory. The most detailed information comes from the work of Mukai and Ohnishi, who allowed mutations to accumulate on Drosophila melanogaster second chromosomes, shielded from selection and recombination by being maintained heterozygous in males. Averaged over studies, the estimated rate of nonlethal viability mutations per second chromosome per generation under an equal-effects model, U BM , was 0.12, suggesting a high genomic mutation rate. We have performed a mutation-accumulation experiment similar to those of Mukai and Ohnishi, except that three large homozygous control populations were maintained. Egg-toadult viability of 72 nonlethal mutation-accumulation (MA) lines and the controls was assayed after 27-33 generations of mutation accumulation. The rate of decline in mean viability was significantly lower than observed by Mukai, and the rate of increase in among-line variance was significantly higher. Our U BM estimate of 0.02 is much lower than the previous estimates. Our results suggest that the rate of mutations that detectably reduce viability may not be much greater than the lethal mutation rate (0.01 in these lines), but the results also are consistent with models that include many mutations with very small effects.The genomic rate and distribution of effects of deleterious mutations are critical parameters in models of the evolution of sex and recombination (1, 2), of the long-term viability of small populations (3, 4), and of molecular and phenotypic variation (5, 6). The classic experiments of Mukai (7,8) and Ohnishi (9) on Drosophila melanogaster, in which mutations were allowed to accumulate on chromosomes shielded from selection and recombination, gave evidence that the rate of mutations with mild negative effects (Ͻ10%) on pre-adult viability is on the order of one per zygote per generation. Among other important consequences, such a high rate of mildly deleterious mutations could doom populations with effective sizes of a few hundred to extinction (3, 10).More recent work, however, has given reason to question whether rates of mutations with detectable effects on fitness traits are typically as high as estimated by Mukai and Ohnishi. Experiments on Drosophila (11) and Caenorhabditis elegans (12) showed much slower declines in fitness traits on relaxation of selection against new mutations than observed by Mukai and Ohnishi. Although methodological differences could explain this discrepancy (13), another possibility is that the mean decline was overestimated in the earlier studies. This could have happened because the studies lacked concurrent controls for viability changes in the mutation-accumulation (MA) lines; viability instead was compared with base generation values that were obtained months earlier. If some change in experimental conditions occurred in the interim that depressed actual or apparent viability, both the mean decline and the genomic mutation rate would hav...

Mutation accumulation and the effect of copia insertions in Drosophila melanogaster

“…Some experimental results suggest that the rate of decline is of the order of 1 % or more per generation (Mukai, 1964 ;Mukai et al, 1972;Shabalina et al, 1997;Fry, 2001), whereas, in another experiment, the rate of decline is much lower (Ferna´ndez & Lo´pez-Fanjul, 1996 ;Chavarrı´as et al, 2001 ;Á vila & Garcı´a-Dorado, 2002). In addition, several authors have raised the possibility that the experiments finding higher rates of decline are flawed in allowing adaptation (Keightley, 1996 ;Garcı´a-Dorado, 1997) or contamination (Houle et al, 1994a) of the control population or that misscoring of flies inflated fitness estimates (Fry et al, 1999). We used a cryopreserved control in a standard MA experiment in hopes that it might help to resolve these uncertainties.…”

“…1 % per generation (Chavarrı´as et al, 2001). Several authors have proposed that biases of various sorts have led to an overestimate of the actual rate of decline in D. melanogaster (Keightley, 1996;Garcı´a-Dorado, 1997 ;Fry et al, 1999) and consequently to an overestimate of U, although some of these claims have been contradicted (Fry, 2001). Analyses that use data showing rapid declines in the mean lead to estimates of U on the order of 0 .…”

Metapopulation extinction caused by mutation accumulation

“…Independent data on a diversity of organisms suggest that the genomic deleterious mutation rate, U, is frequently on the order of 0.1 to 1 per individual per generation in multicellular eukaryotes, and that the average homozygous and heterozygous effects of such mutations are typically less than 5% (26). In flies, data suggest U Ϸ 1, with the average mutation decreasing fitness by about 2% in the heterozygous state (26), although some suggest that U is much smaller, and that the average mutational effect is much larger (27). U may commonly be on the order of 1 in vertebrates and flowering plants (26, 28).…”

Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes

“…20). Second, it was well established that the rate of new lethal mutations in D. melanogaster was Ϸ0.02 per genome per generation (21,22), and it was considered likely that the overall rate of deleterious mutations that are not lethal would be greater than the rate of lethal mutations. Third, the standing genetic variation observed in Drosophila was broadly consistent with the high rate of mutation inferred from Mukai's experiments (23)(24)(25).…”