TY - JOUR
T1 - The role of mutation bias in adaptive molecular evolution
T2 - Insights from convergent changes in protein function
AU - Storz, Jay F.
AU - Natarajan, Chandrasekhar
AU - Signore, Anthony V.
AU - Witt, Christopher C.
AU - McCandlish, David M.
AU - Stoltzfus, Arlin
N1 - Publisher Copyright:
© 2019 The Author(s) Published by the Royal Society. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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'.
AB - 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'.
KW - Adaptation
KW - CpG
KW - Haemoglobin
KW - High altitude
KW - Mutation bias
KW - Protein evolution
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U2 - 10.1098/rstb.2018.0238
DO - 10.1098/rstb.2018.0238
M3 - Article
C2 - 31154983
AN - SCOPUS:85067030527
SN - 0962-8436
VL - 374
JO - Philosophical Transactions of the Royal Society B: Biological Sciences
JF - Philosophical Transactions of the Royal Society B: Biological Sciences
IS - 1777
M1 - 20180238
ER -