Why are deleterious mutations maintained in selfing populations? An analysis of the effects of early- and late-acting mutations by a two-locus two-allele model

2021 ◽  
pp. 110956
Author(s):  
Satoki Sakai
Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 1053-1060
Author(s):  
Joel R Peck

Abstract This study presents a mathematical model that allows for some offspring to be dispersed at random, while others stay close to their mothers. A single genetic locus is assumed to control fertility, and this locus is subject to the occurrence of deleterious mutations. It is shown that, at equilibrium, the frequency of deleterious mutations in the population is inversely related to the rate of dispersal. This is because dispersal of offspring leads to enhanced competition among adults. The results also show that sexual reproduction can lead to a decrease in the equilibrium frequency of deleterious mutations. The reason for this relationship is that sex involves the dispersal of genetic material, and thus, like the dispersal of offspring, sex enhances competition among adults. The model is described using the example of a hermaphroditic plant population. However, the results should apply to animal populations as well.


Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 797-806 ◽  
Author(s):  
James D Fry

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.


Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 2089-2097 ◽  
Author(s):  
Jody Hey

Abstract If multiple linked polymorphisms are under natural selection, then conflicts arise and the efficiency of natural selection is hindered relative to the case of no linkage. This simple interaction between linkage and natural selection creates an opportunity for mutations that raise the level of recombination to increase in frequency and have an enhanced chance of fixation. This important finding by S. Otto and N. Barton means that mutations that raise the recombination rate, but are otherwise neutral, will be selectively favored under fairly general circumstances of multilocus selection and linkage. The effect described by Otto and Barton, which was limited to neutral modifiers, can also be extended to include all modifiers of recombination, both beneficial and deleterious. Computer simulations show that beneficial mutations that also increase recombination have an increased chance of fixation. Similarly, deleterious mutations that also decrease recombination have an increased chance of fixation. The results suggest that a simple model of recombination modifiers, including both neutral and pleiotropic modifiers, is a necessary explanation for the evolutionary origin of recombination.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sankar Subramanian

Abstract Objective Domestication of wild animals results in a reduction in the effective population size, and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to the accumulation of deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using mitochondrial genome data from 364 animals belonging to 18 cattle breeds of the world. Results Our analysis revealed more than a fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the breed age and the proportion of deleterious amino acid-changing polymorphisms. This suggests a proportionally higher deleterious SNPs in young breeds compared to older breeds. Our results highlight the magnitude of difference in the deleterious mutations present in the mitochondrial genomes of various breeds. The results of this study could be useful in predicting the rate of incidence of genetic diseases in different breeds.


Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1991-2001 ◽  
Author(s):  
A García-Dorado ◽  
A Caballero

Abstract T. Mukai and co-workers in the late 1960s and O. Ohnishi in the 1970s carried out a series of experiments to obtain direct estimates of the average coefficient of dominance (h¯) of minor viability mutations in Drosophila melanogaster. The results of these experiments, although inconsistent, have been interpreted as indicating slight recessivity of deleterious mutations, with h¯≈0.4. Mukai obtained conflicting results depending on the type of heterozygotes used, some estimates suggesting overdominance and others partial dominance. Ohnishi's estimates, based on the ratio of heterozygous to homozygous viability declines, were more consistent, pointing to the above value. However, we have reanalyzed Ohnishi's data, estimating h¯ by the regression method, and obtained a much smaller estimate of ~0.1. This significant difference can be due partly to the different weighting implicit in the estimates, but we suggest that this is not the only explanation. We propose as a plausible hypothesis that a putative nonmutational decline in viability occurring in the first half of Ohnishi's experiment (affecting both homozygotes and heterozygotes) has biased upward the estimates from the ratio, while it would not bias the regression estimates. This hypothesis also explains the very high h¯≈0.7 observed in Ohnishi's high-viability chromosomes. By constructing a model of spontaneous mutations using parameters in the literature, we investigate the above possibility. The results indicate that a model of few mutations with moderately large effects and h¯≈0.2 is able to explain the observed estimates and the distributions of homozygous and heterozygous viabilities. Accounting for an expression of mutations in genotypes with the balancer chromosome Cy does not alter the conclusions qualitatively.


Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1893-1906 ◽  
Author(s):  
Jian Li ◽  
Hong-Wen Deng

Abstract The Deng-Lynch method was developed to estimate the rate and effects of deleterious genomic mutations (DGM) in natural populations under the assumption that populations are either completely outcrossing or completely selfing and that populations are at mutation-selection (M-S) balance. However, in many plant and animal populations, selfing or outcrossing is often incomplete in that a proportion of populations undergo inbreeding while the rest are outcrossing. In addition, the degrees of deviation of populations from M-S balance are often not known. Through computer simulations, we investigated the robustness and the applicability of the Deng-Lynch method under different degrees of partial selfing or partial outcrossing and for nonequilibrium populations approaching M-S balance at different stages. The investigation was implemented under constant, variable, and epistatic mutation effects. We found that, generally, the estimation by the Deng-Lynch method is fairly robust if the selfing rate (S) is <0.10 in outcrossing populations and if S > 0.8 in selfing populations. The estimation may be unbiased under partial selfing with variable and epistatic mutation effects in predominantly outcrossing populations. The estimation is fairly robust in nonequilibrium populations at different stages approaching M-S balance. The dynamics of populations approaching M-S balance under various parameters are also studied. Under mutation and selection, populations approach balance at a rapid pace. Generally, it takes 400–2000 generations to reach M-S balance even when starting from homogeneous individuals free of DGM. Our investigation here provides a basis for characterizing DGM in partial selfing or outcrossing populations and for nonequilibrium populations.


Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 497-506 ◽  
Author(s):  
Rasmus Nielsen ◽  
Daniel M Weinreich

Abstract McDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.


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