scholarly journals Evolutionary consequences of mutation and selection within an individual.

Genetics ◽  
1995 ◽  
Vol 141 (3) ◽  
pp. 1173-1187 ◽  
Author(s):  
S P Otto ◽  
M E Orive
Keyword(s):  
Mutation Rate ◽  
Deleterious Mutation ◽  
Cell Lineage ◽  
Deleterious Mutations ◽  
Cell Replication ◽  
Mutation Load ◽  
Ploidy Levels ◽  
Cell Lineages ◽  
Evolutionary Consequences ◽  
Mutant Cells

Abstract Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective "deaths" necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.

scholarly journals Harmful mutation load in the mitochondrial genomes of cattle breeds

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sankar Subramanian
Keyword(s):  
Population Size ◽  
Artificial Selection ◽  
Deleterious Mutation ◽  
Genetic Diseases ◽  
Mitochondrial Genomes ◽  
Deleterious Mutations ◽  
Founder Population ◽  
Mutation Load ◽  
Effective Population ◽  
Cattle Breeds

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.

scholarly journals The mutation load under tetrasomic inheritance and its consequences for the evolution of the selfing rate in autotetraploid species

1999 ◽  
Vol 74 (1) ◽  
pp. 31-42 ◽  
Author(s):  
J. RONFORT
Keyword(s):  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Stable State ◽  
Approximate Solutions ◽  
Balance Model ◽  
Deleterious Mutations ◽  
Selfing Rate ◽  
Mutation Load ◽  
Mean Fitness ◽  
The Mean

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

scholarly journals A deleterious mutation-sheltering theory for the evolution of sex chromosomes and supergenes

2021 ◽  
Author(s):  
Paul Jay ◽  
Tatiana Giraud ◽  
Emilie Tezenas
Keyword(s):  
Mathematical Modeling ◽  
Sex Chromosomes ◽  
Deleterious Mutation ◽  
Stochastic Simulations ◽  
Recessive Mutation ◽  
Deleterious Mutations ◽  
Evolution Of Sex ◽  
Mutation Load ◽  
Recombination Suppression ◽  
Chromosomal Inversions

Many organisms have sex chromosomes with large non-recombining regions having expanded stepwise, the reason why being still poorly understood. Theories proposed so far rely on differences between sexes but are poorly supported by empirical data and cannot account for the stepwise suppression of recombination around sex chromosomes in organisms without sexual dimorphism. We show here, by mathematical modeling and stochastic simulations, that recombination suppression in sex chromosomes can evolve simply because it shelters recessive deleterious mutations, which are ubiquitous in genomes. The permanent heterozygosity of sex-determining alleles protects linked chromosomal inversions against expression of their recessive mutation load, leading to an accumulation of inversions around these loci, as observed in nature. We provide here a testable and widely applicable theory to explain the evolution of sex chromosomes and of supergenes in general.

scholarly journals Harmful Mutation Load in the Mitochondrial Genomes of Cattle Breeds 

2021 ◽  
Author(s):  
Sankar Subramanian
Keyword(s):  
Amino Acid ◽  
Population Size ◽  
Artificial Selection ◽  
Deleterious Mutation ◽  
Mitochondrial Genomes ◽  
Deleterious Mutations ◽  
Founder Population ◽  
Mutation Load ◽  
Effective Population ◽  
Cattle Breeds

Abstract ObjectiveDomestication 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 accumulation 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 252 animals belonging to 15 cattle breeds of the world. ResultsOur analysis revealed more than fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the neutral heterozygosity and the ratio of amino acid changing diversity to silent diversity. This suggests a proportionally higher amino acid changing variants in breeds with low diversity. 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.

scholarly journals The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Katia Koelle ◽  
David A Rasmussen
Keyword(s):  
Influenza Virus ◽  
Genetic Linkage ◽  
Influenza A ◽  
Deleterious Mutation ◽  
Rna Virus ◽  
Phylogenetic Analyses ◽  
Molecular Pathways ◽  
Deleterious Mutations ◽  
Mutation Load ◽  
Antigenic Evolution

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

scholarly journals The Effect of Overdominance on Characterizing Deleterious Mutations in Large Natural Populations

Genetics ◽  
1999 ◽  
Vol 151 (2) ◽  
pp. 895-913 ◽  
Author(s):  
Jin-Long Li ◽  
Jian Li ◽  
Hong-Wen Deng
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
Statistical Properties ◽  
Alternative Methods ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
New Approaches

Abstract Alternatives to the mutation-accumulation approach have been developed to characterize deleterious genomic mutations. However, they all depend on the assumption that the standing genetic variation in natural populations is solely due to mutation-selection (M-S) balance and therefore that overdominance does not contribute to heterosis. Despite tremendous efforts, the extent to which this assumption is valid is unknown. With different degrees of violation of the M-S balance assumption in large equilibrium populations, we investigated the statistical properties and the robustness of these alternative methods in the presence of overdominance. We found that for dominant mutations, estimates for U (genomic mutation rate) will be biased upward and those for h̄ (mean dominance coefficient) and s̄ (mean selection coefficient), biased downward when additional overdominant mutations are present. However, the degree of bias is generally moderate and depends largely on the magnitude of the contribution of overdominant mutations to heterosis or genetic variation. This renders the estimates of U and s̄ not always biased under variable mutation effects that, when working alone, cause U and s̄ to be underestimated. The contributions to heterosis and genetic variation from overdominant mutations are monotonic but not linearly proportional to each other. Our results not only provide a basis for the correct inference of deleterious mutation parameters from natural populations, but also alleviate the biggest concern in applying the new approaches, thus paving the way for reliably estimating properties of deleterious mutations.

scholarly journals Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex

2019 ◽  
Author(s):  
Christine Grossen ◽  
Frederic Guillaume ◽  
Lukas F. Keller ◽  
Daniel Croll
Keyword(s):  
Deleterious Mutation ◽  
Conservation Status ◽  
Population Bottlenecks ◽  
Deleterious Mutations ◽  
Population Declines ◽  
Mutation Load ◽  
Current Conservation ◽  
Term Survival ◽  
Alpine Ibex ◽  
Species Survival

AbstractHuman activity caused dramatic population declines in many wild species. The resulting bottlenecks have a profound impact on the genetic makeup of a species with unknown consequences for health. A key genetic factor for species survival is the evolution of deleterious mutation load, but how bottleneck strength and mutation load interact lacks empirical evidence. Here, we take advantage of the exceptionally well-characterized population bottlenecks of the once nearly extinct Alpine ibex. The species survived one of the most dramatic bottlenecks known for successfully restored species. We analyze 60 complete genomes of six ibex species and the domestic goat. We show that historic bottlenecks rather than the current conservation status predict levels of genome-wide variation. By retracing the recolonization of the Alps by Alpine ibex, we find genomic evidence of concurrent purging of highly deleterious mutations but accumulation of mildly deleterious mutations. This demonstrates how human-induced severe bottlenecks caused both relaxed selection and purging, thus reshaping the landscape of deleterious mutation load. Our findings also highlight that even populations of ~1000 individuals can accumulate mildly deleterious mutations. Hence, conservation efforts should focus on preventing population declines below such levels to ensure long-term survival of species.

scholarly journals Genetic linkage and natural selection

2010 ◽  
Vol 365 (1552) ◽  
pp. 2559-2569 ◽  
Author(s):  
N. H. Barton
Keyword(s):  
Deleterious Mutation ◽  
Balancing Selection ◽  
Selective Sweeps ◽  
Deleterious Mutations ◽  
Mutation Load ◽  
Random Drift ◽  
Selection For ◽  
Genomic Regions ◽  
Significant Interference ◽  
General Explanation

The prevalence of recombination in eukaryotes poses one of the most puzzling questions in biology. The most compelling general explanation is that recombination facilitates selection by breaking down the negative associations generated by random drift (i.e. Hill–Robertson interference, HRI). I classify the effects of HRI owing to: deleterious mutation, balancing selection and selective sweeps on: neutral diversity, rates of adaptation and the mutation load. These effects are mediated primarily by the density of deleterious mutations and of selective sweeps. Sequence polymorphism and divergence suggest that these rates may be high enough to cause significant interference even in genomic regions of high recombination. However, neither seems able to generate enough variance in fitness to select strongly for high rates of recombination. It is plausible that spatial and temporal fluctuations in selection generate much more fitness variance, and hence selection for recombination, than can be explained by uniformly deleterious mutations or species-wide selective sweeps.

scholarly journals Dynamics and fate of beneficial mutations under lineage contamination by linked deleterious mutations

2016 ◽  
Author(s):  
Sophie Pénisson ◽  
Tanya Singh ◽  
Paul Sniegowski ◽  
Philip Gerrish
Keyword(s):  
Mutation Rate ◽  
Branching Process ◽  
Deleterious Mutation ◽  
Selective Advantage ◽  
Single Type ◽  
Deleterious Mutations ◽  
Beneficial Mutations ◽  
Multitype Branching Process ◽  
Fitness Effects ◽  
Adaptive Substitution

ABSTRACTBeneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly-arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly-arising beneficial mutation as a multitype branching process; this approach allows us to account for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination. We first study the lineage contamination phenomenon in isolation, deriving extinction times and probabilities of beneficial lineages. We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that the survival probability of beneficial mutations is simply Haldane’s classical formula multiplied by the correction factor , where U is deleterious mutation rate, is mean selective advantage of beneficial mutations, κ ∈ (1, ε], and ε = 2 – e−1. We also find there exists a genomic deleterious mutation rate, , that maximizes the rate of production of surviving beneficial mutations, and that . Both of these results, and others, are curiously independent of the fitness effects of deleterious mutations. We derive critical mutation rates above which: 1) lineage contamination alleviates competition among beneficial mutations, and 2) the adaptive substitution process all but shuts down.

scholarly journals Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli

2010 ◽  
Vol 365 (1544) ◽  
pp. 1177-1186 ◽  
Author(s):  
Sandra Trindade ◽  
Lilia Perfeito ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Estimation Methods ◽  
Single Individual ◽  
Deleterious Mutations ◽  
Spontaneous Mutations ◽  
Mutator Strain ◽  
Mean Fitness

Knowledge of the mutational parameters that affect the evolution of organisms is of key importance in understanding the evolution of several characteristics of many natural populations, including recombination and mutation rates. In this study, we estimated the rate and mean effect of spontaneous mutations that affect fitness in a mutator strain of Escherichia coli and review some of the estimation methods associated with mutation accumulation (MA) experiments. We performed an MA experiment where we followed the evolution of 50 independent mutator lines that were subjected to repeated bottlenecks of a single individual for approximately 1150 generations. From the decline in mean fitness and the increase in variance between lines, we estimated a minimum mutation rate to deleterious mutations of 0.005 (±0.001 with 95% confidence) and a maximum mean fitness effect per deleterious mutation of 0.03 (±0.01 with 95% confidence). We also show that any beneficial mutations that occur during the MA experiment have a small effect on the estimate of the rate and effect of deleterious mutations, unless their rate is extremely large. Extrapolating our results to the wild-type mutation rate, we find that our estimate of the mutational effects is slightly larger and the inferred deleterious mutation rate slightly lower than previous estimates obtained for non-mutator E. coli .

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