1 School of Biological Sciences, University of Nebraska , Lincoln, NE 68588 , USA.
2 Department of Biology, University of New Mexico , Albuquerque, NM 87131 , USA.
Philos Trans R Soc Lond B Biol Sci. 2019 Jul 22;374(1777):20180238. doi: 10.1098/rstb.2018.0238. Epub 2019 Jun 3.
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'.
进化遗传学中一个尚未得到充分探讨的问题是，产生遗传变异的突变偏向在多大程度上影响适应性分子进化的结果和途径。在至少一些脊椎动物类群的基因组中，一种重要的突变偏向形式涉及 CpG 二核苷酸的变化：如果 DNA 核苷酸胞嘧啶 (C) 在同一编码链上紧邻鸟嘌呤 (G)，则这两个位点的点突变发生的频率相对于非 CpG 位点的突变会升高，这取决于甲基化状态。在这里，我们检查了来自案例研究的实验数据，在这些研究中，已经有可能确定导致脊椎动物血红蛋白 (Hb) 功能特性适应性变化的因果替换。具体来说，我们研究了高海拔鸟类 Hb-O 亲和力趋同增加的分子基础。我们使用一组在高海拔鸟类 Hb 中经过实验验证的、可增强亲和力的突变数据集，检验了因果变化是否相对于所有可能的错义突变中 CpG 突变的频率，富集了 CpG 二核苷酸的突变。测试结果表明，不成比例数量的因果氨基酸替换归因于 CpG 突变，这表明突变偏向可以影响分子适应的结果。本文是主题为“基因组时代的趋同进化：新的见解和方向”的一部分。
