Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens
Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens
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DOI：
10.1073/pnas.1507300112
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发表时间：
2015-11-10
影响因子：
11.1
通讯作者：
Witt, Christopher C.
中科院分区：
文献类型：
--
作者：
Galen, Spencer C.;Natarajan, Chandrasekhar;Witt, Christopher C.
进化遗传学中的一个关键问题是为什么某些突变或某些类型的突变对适应性表型进化的贡献不成比例。原则上，特定突变的优先固定可能直接源于改变功能的等位基因的潜在突变率的变化。然而，突变偏倚对表型进化遗传结构的影响很难评估，因为很少有关于功能改变等位基因突变率的数据。在这里，我们报告的发现，在一个高度可变的网站在β（A）-珠蛋白基因的单点突变有助于血红蛋白（Hb）功能的进化变化在高海拔安第斯弗伦斯（Troglodytes aedon）。对天然Hb变体和工程化重组Hb突变体的实验结果表明，β（A）-珠蛋白基因中CpG二核苷酸的非同义突变是造成高海拔和低海拔家鹪鹩种群之间Hb-O-2亲和力进化差异的原因。此外，高海拔和低海拔人群之间的基因组分化模式表明，在致病氨基酸多态性的等位基因频率的海拔分化反映了历史的空间变化的选择。实验结果突出的表型进化的遗传基础上的突变率的影响表明，一个大的影响等位基因在一个高度可变的CpG位点促进了生理分化的血O-2的运输能力之间的家鹪鹩种群是本地不同的海拔。
A key question in evolutionary genetics is why certain mutations or certain types of mutation make disproportionate contributions to adaptive phenotypic evolution. In principle, the preferential fixation of particular mutations could stem directly from variation in the underlying rate of mutation to function-altering alleles. However, the influence of mutation bias on the genetic architecture of phenotypic evolution is difficult to evaluate because data on rates of mutation to function-altering alleles are seldom available. Here, we report the discovery that a single point mutation at a highly mutable site in the beta(A)-globin gene has contributed to an evolutionary change in hemoglobin (Hb) function in high-altitude Andean house wrens (Troglodytes aedon). Results of experiments on native Hb variants and engineered, recombinant Hb mutants demonstrate that a nonsynonymous mutation at a CpG dinucleotide in the beta(A)-globin gene is responsible for an evolved difference in Hb-O-2 affinity between high-and low-altitude house wren populations. Moreover, patterns of genomic differentiation between high-and low-altitude populations suggest that altitudinal differentiation in allele frequencies at the causal amino acid polymorphism reflects a history of spatially varying selection. The experimental results highlight the influence of mutation rate on the genetic basis of phenotypic evolution by demonstrating that a large-effect allele at a highly mutable CpG site has promoted physiological differentiation in blood O-2 transport capacity between house wren populations that are native to different elevations.