The deleterious mutation load is insensitive to recent population history

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.

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Nature of Deleterious Mutation Load in Drosophila

Genetics ◽

10.1093/genetics/144.4.1993 ◽

1996 ◽

Vol 144 (4) ◽

pp. 1993-1999 ◽

Cited By ~ 5

Author(s):

Peter D Keightley

Keyword(s):

Deleterious Mutation ◽

Spontaneous Mutation ◽

Mutation Accumulation ◽

Mutation Rates ◽

Mutation Load ◽

Spontaneous Mutation Rate ◽

A Minor ◽

Chromosome I ◽

Balancer Chromosomes ◽

Balancer Chromosome

Much population genetics and evolution theory depends on knowledge of genomic mutation rates and distributions of mutation effects for fitness, but most information comes from a few mutation accumulation experiments in Drosophila in which replicated chromosomes are sheltered from natural selection by a balancer chromosome. I show here that data from these experiments imply the existence of a large class of minor viability mutations with approximately equivalent effects. However, analysis of the distribution of viabilities of chromosomes exposed to EMS mutagenesis reveals a qualitatively different distribution of effects lacking such a minor effects class. A possible explanation for this difference is that transposable element insertions, a common class of spontaneous mutation event in Drosophila, frequently generate minor viability effects. This explanation would imply that current estimates of deleterious mutation rates are not generally applicable in evolutionary models, as transposition rates vary widely. Alternatively, much of the apparent decline in viability under spontaneous mutation accumulation could have been nonmutational, perhaps due to selective improvement of balancer chromosomes. This explanation accords well with the data and implies a spontaneous mutation rate for viability two orders of magnitude lower than previously assumed, with most mutation load attributable to major effects.

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

Genetics Research ◽

10.1017/s0016672399003845 ◽

1999 ◽

Vol 74 (1) ◽

pp. 31-42 ◽

Cited By ~ 59

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.

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Demographic history shaped geographical patterns of deleterious mutation load in a broadly distributed Pacific Salmon

PLoS Genetics ◽

10.1371/journal.pgen.1008348 ◽

2020 ◽

Vol 16 (8) ◽

pp. e1008348 ◽

Cited By ~ 2

Author(s):

Quentin Rougemont ◽

Jean-Sébastien Moore ◽

Thibault Leroy ◽

Eric Normandeau ◽

Eric B. Rondeau ◽

...

Keyword(s):

Deleterious Mutation ◽

Pacific Salmon ◽

Demographic History ◽

Mutation Load ◽

Geographical Patterns

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SEX-CHROMOSOME TURNOVERS INDUCED BY DELETERIOUS MUTATION LOAD

Evolution ◽

10.1111/j.1558-5646.2012.01810.x ◽

2012 ◽

Vol 67 (3) ◽

pp. 635-645 ◽

Cited By ~ 49

Author(s):

Olivier Blaser ◽

Christine Grossen ◽

Samuel Neuenschwander ◽

Nicolas Perrin

Keyword(s):

Sex Chromosome ◽

Deleterious Mutation ◽

Mutation Load

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Human Spermatogenic Failure Purges Deleterious Mutation Load from the Autosomes and Both Sex Chromosomes, including the Gene DMRT1

PLoS Genetics ◽

10.1371/journal.pgen.1003349 ◽

2013 ◽

Vol 9 (3) ◽

pp. e1003349 ◽

Cited By ~ 84

Author(s):

Alexandra M. Lopes ◽

Kenneth I. Aston ◽

Emma Thompson ◽

Filipa Carvalho ◽

João Gonçalves ◽

...

Keyword(s):

Sex Chromosomes ◽

Deleterious Mutation ◽

Mutation Load ◽

Spermatogenic Failure

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

eLife ◽

10.7554/elife.07361 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 41

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.

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Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution

Molecular Biology and Evolution ◽

10.1093/molbev/msm001 ◽

2007 ◽

Vol 24 (3) ◽

pp. 845-852 ◽

Cited By ~ 100

Author(s):

Oliver G. Pybus ◽

Andrew Rambaut ◽

Robert Belshaw ◽

Robert P. Freckleton ◽

Alexei J. Drummond ◽

...

Keyword(s):

Deleterious Mutation ◽

Rna Viruses ◽

Viral Evolution ◽

Mutation Load

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