The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function.

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TitleThe role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function.
Publication TypeJournal Article
Year of Publication2019
AuthorsStorz, JF, Natarajan, C, Signore, AV, Witt, CC, McCandlish, DM, Stoltzfus, A
JournalPhilos Trans R Soc Lond B Biol Sci
Volume374
Issue1777
Pagination20180238
Date Published2019 Jul 22
ISSN1471-2970
Abstract

An underexplored question in evolutionary genetics concerns the extent to which mutational bias in the production of genetic variation influences outcomes and pathways of adaptive molecular evolution. In the genomes of at least some vertebrate taxa, an important form of mutation bias involves changes at CpG dinucleotides: if the DNA nucleotide cytosine (C) is immediately 5' to guanine (G) on the same coding strand, then-depending on methylation status-point mutations at both sites occur at an elevated rate relative to mutations at non-CpG sites. Here, we examine experimental data from case studies in which it has been possible to identify the causative substitutions that are responsible for adaptive changes in the functional properties of vertebrate haemoglobin (Hb). Specifically, we examine the molecular basis of convergent increases in Hb-O affinity in high-altitude birds. Using a dataset of experimentally verified, affinity-enhancing mutations in the Hbs of highland avian taxa, we tested whether causative changes are enriched for mutations at CpG dinucleotides relative to the frequency of CpG mutations among all possible missense mutations. The tests revealed that a disproportionate number of causative amino acid replacements were attributable to CpG mutations, suggesting that mutation bias can influence outcomes of molecular adaptation. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.

DOI10.1098/rstb.2018.0238
Alternate JournalPhilos. Trans. R. Soc. Lond., B, Biol. Sci.
PubMed ID31154983
PubMed Central IDPMC6560279