Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose.
Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose.
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DOI：
10.1371/journal.pgen.1007331
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发表时间：
2018-04
期刊：
影响因子：
4.5
通讯作者：
Storz JF
中科院分区：
文献类型：
--
作者：
Natarajan C;Jendroszek A;Kumar A;Weber RE;Tame JRH;Fago A;Storz JF
在特定性状的适应性进化过程中，一些选择性固定突变可能是直接导致的，而另一些可能是纯粹的补偿性突变。这两类突变对适应性表型进化的相对贡献取决于突变多效性的形式和流行程度。为了研究适应性取代的性质及其多向性效应，我们使用蛋白质工程方法表征了高飞斑头雁（Anser indicus）血红蛋白（Hb）适应的分子基础，斑头雁是一种以跨喜马拉雅迁徙而闻名的耐缺氧物种。为了检验所观察到的替代对进化相关遗传背景的影响，我们合成了野生型斑头鹅基因型与斑头鹅最近的共同祖先及其低地亲缘关系的所有可能的基因型中间体。定点诱变实验显示，在所有可能的遗传背景下，一个主要效应突变显著增加了Hb-O2亲和力。另外两个突变在不同背景下表现出较小的平均效应大小和较小的可加性。后一种突变产生了伴随的自氧化率增加，这是一种有害的副作用，由空间上近端残基的第二位点突变完全补偿。实验揭示了三个关键的见解：(i)细微的、局部的结构变化可以产生巨大的功能效应；（ii）改变功能的突变的相对效应大小可能取决于它们发生的先后顺序；(3)对有害多效效应的补偿可能在蛋白质功能的适应性进化中起重要作用。在适应性表型进化过程中，一些相关的遗传变化可能直接导致所选性状的变化（致病突变），而其他变化可能改善致病变化的负面副作用（代偿突变）。为了评估这种变化的性质及其相对普遍性，我们使用蛋白质工程方法来表征一种有充分记录的生化适应的分子基础：在高海拔飞行冠军斑头雁（Anser indicus）中增加的血红蛋白-氧亲和力。实验揭示了特异性取代对斑头雁血红蛋白-氧亲和力适应性增加的贡献，并证明了代偿性相互作用可能在适应性蛋白进化中发挥重要作用，这是由于不同功能特性之间的权衡。
During the adaptive evolution of a particular trait, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation to adaptive phenotypic evolution depends on the form and prevalence of mutational pleiotropy. To investigate the nature of adaptive substitutions and their pleiotropic effects, we used a protein engineering approach to characterize the molecular basis of hemoglobin (Hb) adaptation in the high-flying bar-headed goose (Anser indicus), a hypoxia-tolerant species renowned for its trans-Himalayan migratory flights. To test the effects of observed substitutions on evolutionarily relevant genetic backgrounds, we synthesized all possible genotypic intermediates in the line of descent connecting the wildtype bar-headed goose genotype with the most recent common ancestor of bar-headed goose and its lowland relatives. Site-directed mutagenesis experiments revealed one major-effect mutation that significantly increased Hb-O2 affinity on all possible genetic backgrounds. Two other mutations exhibited smaller average effect sizes and less additivity across backgrounds. One of the latter mutations produced a concomitant increase in the autoxidation rate, a deleterious side-effect that was fully compensated by a second-site mutation at a spatially proximal residue. The experiments revealed three key insights: (i) subtle, localized structural changes can produce large functional effects; (ii) relative effect sizes of function-altering mutations may depend on the sequential order in which they occur; and (iii) compensation of deleterious pleiotropic effects may play an important role in the adaptive evolution of protein function. During adaptive phenotypic evolution, some of the associated genetic changes may contribute directly to changes in the selected trait (causative mutations) and other changes may ameliorate the negative side-effects of the causative changes (compensatory mutations). To assess the nature of such changes and their relative prevalence, we used a protein engineering approach to characterize the molecular basis of a well-documented biochemical adaptation: the increased hemoglobin-oxygen affinity in the bar-headed goose (Anser indicus), a champion of high-altitude flight. The experiments revealed the contributions of specific substitutions to the adaptive increase in hemoglobin-oxygen affinity in bar-headed goose and demonstrated that compensatory interactions may play an important role in adaptive protein evolution due to trade-offs between different functional properties.
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DOI：
10.1073/pnas.1507300112
发表时间：
2015-11-10
影响因子：
11.1
作者：
Galen, Spencer C.;Natarajan, Chandrasekhar;Witt, Christopher C.
通讯作者：
Witt, Christopher C.
DOI：
10.1073/pnas.91.24.11547
发表时间：
1994-11-22
影响因子：
11.1
作者：
KIM, HW;SHEN, TJ;HO, C
通讯作者：
HO, C
影响因子：
4.8
作者：
Birukou, Ivan;Schweers, Rachel L.;Olson, John S.
通讯作者：
Olson, John S.
影响因子：
3.3
作者：
BENCOWITZ, HZ;WAGNER, PD;WEST, JB
通讯作者：
WEST, JB
DOI：
10.1016/0034-5687(80)90046-8
发表时间：
1980-01-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
BLACK, CP;TENNEY, SM
通讯作者：
TENNEY, SM