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Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations.

ABSTRACT: Linked beneficial and deleterious mutations are known to decrease the fixation probability of a favorable mutation in large asexual populations. While the hindering effect of strongly deleterious mutations on adaptive evolution has been well studied, how weakly deleterious mutations, either in isolation or with superior beneficial mutations, influence the rate of adaptation has not been fully explored. When the selection against the deleterious mutations is weak, the beneficial mutant can fix in many genetic backgrounds, besides the one it arose on. Here, taking this factor into account, I obtain an accurate analytical expression for the fixation probability of a beneficial mutant in an asexual population at mutation-selection balance. I then exploit this result along with clonal interference theory to investigate the joint effect of linked beneficial and deleterious mutations on the rate of adaptation, and identify parameter regions where it is reduced due to interference by either beneficial or deleterious or both types of mutations. I also study the evolution of mutation rates in adapting asexual populations, and find that linked beneficial mutations have a stronger influence than the deleterious mutations on mutator fixation.

SUBMITTER: Jain K

PROVIDER: S-EPMC6456326 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations.

Jain Kavita K

Genetics 20190130 4

Linked beneficial and deleterious mutations are known to decrease the fixation probability of a favorable mutation in large asexual populations. While the hindering effect of strongly deleterious mutations on adaptive evolution has been well studied, how weakly deleterious mutations, either in isolation or with superior beneficial mutations, influence the rate of adaptation has not been fully explored. When the selection against the deleterious mutations is weak, the beneficial mutant can fix in ...[more]

PMID: 30700529

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Project description:Beneficial 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. Our approach accounts 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 dynamics and survival probabilities (the complement of extinction probabilities) of beneficial lineages. We find that survival probability is zero when [Formula: see text] where U is deleterious mutation rate and [Formula: see text] is the selective advantage of the beneficial mutation in question, and is otherwise depressed below classical predictions by a factor bounded from below by [Formula: see text] We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that, under the combined effects of lineage contamination and background selection, ensemble survival probability is never zero but is depressed below classical predictions by a factor bounded from below by [Formula: see text] where [Formula: see text] is mean selective advantage of beneficial mutations, and [Formula: see text] This factor, and other bounds derived from it, are independent of the fitness effects of deleterious mutations. At high enough mutation rates, lineage contamination can depress fixation probabilities to values that approach zero. This fact suggests that high mutation rates can, perhaps paradoxically, (1) alleviate competition among beneficial mutations, or (2) potentially even shut down the adaptive process. We derive critical mutation rates above which these two events become likely.

Dataset Information

Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations.

Publications

Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations.

Similar Datasets

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