Epistasis and natural selection shape the mutational architecture of complex traits

The evolutionary trajectories of complex traits are constrained by levels of genetic variation as well as genetic correlations among traits. As the ultimate source of all genetic variation is mutation, the distribution of mutations entering populations profoundly affects standing variation and genet...

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Bibliographic Details
Published in:Nature communications 2014-05, Vol.5 (1), p.3709-3709, Article 3709
Main Authors: Jones, Adam G., Bürger, Reinhard, Arnold, Stevan J.
Format: Article
Language:English
Subjects:
631/181
631/208/2490/1472
631/208/737
Alzheimer's disease
Computer Simulation
Epistasis, Genetic
Evolution
Evolution, Molecular
Gene loci
Genetic Variation
Genotype
Genotype & phenotype
Humanities and Social Sciences
Humans
Models, Genetic
multidisciplinary
Multifactorial Inheritance
Mutation
Phenotype
Quantitative genetics
Science
Science (multidisciplinary)
Selection, Genetic
Simulation
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Summary:The evolutionary trajectories of complex traits are constrained by levels of genetic variation as well as genetic correlations among traits. As the ultimate source of all genetic variation is mutation, the distribution of mutations entering populations profoundly affects standing variation and genetic correlations. Here we use an individual-based simulation model to investigate how natural selection and gene interactions (that is, epistasis) shape the evolution of mutational processes affecting complex traits. We find that the presence of epistasis allows natural selection to mould the distribution of mutations, such that mutational effects align with the selection surface. Consequently, novel mutations tend to be more compatible with the current forces of selection acting on the population. These results suggest that in many cases mutational effects should be seen as an outcome of natural selection rather than as an unbiased source of genetic variation that is independent of other evolutionary processes. Mutations are the source of genetic variation, yet the mechanisms determining the distribution of mutations are unclear. Here, Jones et al. show that gene interactions allow natural selection to shape the distribution of mutations, suggesting that mutations can be a biased source of genetic variation.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms4709