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Causes of molecular convergence and parallelism in protein evolution

Causes of molecular convergence and parallelism in protein evolution An important question in evolutionary genetics concerns the extent to which adaptive convergence in protein function is caused by convergent or parallel changes at the amino acid level. Even when there is a many-to-one mapping of genotype to phenotype, particular mutations may be preferentially fixed (substitution bias) owing to among-site variation in the rate of mutation to function-altering alleles and/or variation among mutations in their probability of fixation once they arise. Within the set of mutations that have functionally equivalent effects on a selected phenotype, those that incur a lower magnitude of deleterious pleiotropy will generally have higher fixation probabilities. Mutational pleiotropy may therefore represent an important source of substitution bias. A key finding is that the fitness effects of amino acid mutations are often conditional on the genetic background in which they occur. This context dependence (epistasis) reduces the probability of molecular convergence and parallelism because it reduces the number of possible mutations that have unconditionally acceptable effects in divergent genetic backgrounds. Context-dependent mutational effects often stem from pleiotropic trade-offs, as evidenced by cases where the fitness impact of a given mutation is determined by compensatory (conditionally beneficial) mutations at other sites in the same protein. Even if mutations have identical functional effects on a selected phenotype, they can have different fitness effects owing to a nonlinear mapping of phenotype to fitness. Thus, probabilities of convergence and parallelism are reduced by species differences in the genotype-phenotype map and by differences in the phenotype-fitness map. Although computational analyses of sequence variation play a key part in suggesting hypotheses about the causes of convergent and parallel substitutions and their possible adaptive significance, experimental analyses of specific mutations are necessary to test such hypotheses. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Genetics Springer Journals

Causes of molecular convergence and parallelism in protein evolution

Nature Reviews Genetics , Volume 17 (4) – Mar 14, 2016

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References (141)

Publisher
Springer Journals
Copyright
Copyright © 2016 by Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1471-0056
eISSN
1471-0064
DOI
10.1038/nrg.2016.11
Publisher site
See Article on Publisher Site

Abstract

An important question in evolutionary genetics concerns the extent to which adaptive convergence in protein function is caused by convergent or parallel changes at the amino acid level. Even when there is a many-to-one mapping of genotype to phenotype, particular mutations may be preferentially fixed (substitution bias) owing to among-site variation in the rate of mutation to function-altering alleles and/or variation among mutations in their probability of fixation once they arise. Within the set of mutations that have functionally equivalent effects on a selected phenotype, those that incur a lower magnitude of deleterious pleiotropy will generally have higher fixation probabilities. Mutational pleiotropy may therefore represent an important source of substitution bias. A key finding is that the fitness effects of amino acid mutations are often conditional on the genetic background in which they occur. This context dependence (epistasis) reduces the probability of molecular convergence and parallelism because it reduces the number of possible mutations that have unconditionally acceptable effects in divergent genetic backgrounds. Context-dependent mutational effects often stem from pleiotropic trade-offs, as evidenced by cases where the fitness impact of a given mutation is determined by compensatory (conditionally beneficial) mutations at other sites in the same protein. Even if mutations have identical functional effects on a selected phenotype, they can have different fitness effects owing to a nonlinear mapping of phenotype to fitness. Thus, probabilities of convergence and parallelism are reduced by species differences in the genotype-phenotype map and by differences in the phenotype-fitness map. Although computational analyses of sequence variation play a key part in suggesting hypotheses about the causes of convergent and parallel substitutions and their possible adaptive significance, experimental analyses of specific mutations are necessary to test such hypotheses.

Journal

Nature Reviews GeneticsSpringer Journals

Published: Mar 14, 2016

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