The role of mutation bias in adaptive molecular evolution

Insights from convergent changes in protein function

Jay F Storz, Chandrasekhar Natarajan, Anthony V. Signore, Christopher C. Witt, David M. McCandlish, Arlin Stoltzfus

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 50 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-O2 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'.

Original languageEnglish (US)
Article number20180238
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume374
Issue number1777
DOIs
StatePublished - Jan 1 2019

Fingerprint

Molecular Evolution
Hemoglobins
Cytosine Nucleotides
mutation
Mutation
Methylation
Guanine
Birds
Proteins
Substitution reactions
proteins
Genes
Amino Acids
Vertebrates
DNA
hemoglobin
vertebrates
Mutation Rate
Missense Mutation
missense mutation

Keywords

  • Adaptation
  • CpG
  • Haemoglobin
  • High altitude
  • Mutation bias
  • Protein evolution

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The role of mutation bias in adaptive molecular evolution : Insights from convergent changes in protein function. / Storz, Jay F; Natarajan, Chandrasekhar; Signore, Anthony V.; Witt, Christopher C.; McCandlish, David M.; Stoltzfus, Arlin.

In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 374, No. 1777, 20180238, 01.01.2019.

Research output: Contribution to journalArticle

Storz, Jay F ; Natarajan, Chandrasekhar ; Signore, Anthony V. ; Witt, Christopher C. ; McCandlish, David M. ; Stoltzfus, Arlin. / The role of mutation bias in adaptive molecular evolution : Insights from convergent changes in protein function. In: Philosophical Transactions of the Royal Society B: Biological Sciences. 2019 ; Vol. 374, No. 1777.
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