Storz, J. F., Natarajan, C., Signore, A. V., Witt, C. C., McCandlish, D. M., Stoltzfus, A. (July 2019) The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function. Philos Trans R Soc Lond B Biol Sci, 374 (1777). p. 20180238. ISSN 0962-8436 (Public Dataset)
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-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'.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal organism description > animal > bird bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > CpG islands evolution bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations |
| CSHL Authors: | |
| Communities: | CSHL labs > McCandlish lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: | Matthew Dunn |
| Date: | 22 July 2019 |
| Date Deposited: | 06 Jun 2019 20:03 |
| Last Modified: | 02 Feb 2024 20:59 |
| PMCID: | PMC6560279 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/38067 |
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