The molecular basis of high-altitude adaptation in deer mice.
The molecular basis of high-altitude adaptation in deer mice.
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DOI：
10.1371/journal.pgen.0030045
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发表时间：
2007-03-30
期刊：
影响因子：
4.5
通讯作者：
Nachman MW
中科院分区：
文献类型：
--
作者：
Storz JF;Sabatino SJ;Hoffmann FG;Gering EJ;Moriyama H;Ferrand N;Monteiro B;Nachman MW
阐明适应的遗传机制是进化生物学的一个重要目标，但很少有实证研究成功地记录了自然种群中分子变异和生物体适应性之间的因果关系。在这里，我们报告了一个两个位点的α-珠蛋白多态性的群体遗传学分析，该多态性是鹿鼠，Peromyscus maniculatus的自然群体对高海拔缺氧的生理适应的基础。该系统提供了一个难得的机会，以检查蛋白质功能的适应性相关的变化，可以与一个明确的选择压力的分子基础。我们调查了来自高海拔和低海拔地区的Maniculatus的重复α-珠蛋白基因的DNA序列变异，以（i）确定可能导致血红蛋白功能差异微调的特定突变，（ii）测试基因是否表现出居住在不同海拔地区的种群之间多样化选择的预期特征。结果表明，功能不同的蛋白质等位基因保持作为一个长期的平衡的多态性和血红蛋白功能的适应性修改产生的独立或联合作用的5个氨基酸突变，调节氧结合亲和力。进化生物学的一个主要目标是确定使生物体能够适应其环境的特定遗传机制。鹿鼠血红蛋白的变化代表了一个特别有前途的系统，用于研究适应的分子基础，因为它已经有可能建立蛋白质功能的等位基因变异和生理性能的适应性相关变异之间的机制联系。具体而言，来自不同海拔的小鼠在血液生化和有氧代谢方面的适应性变异与编码成人血红蛋白α链亚基的两个紧密连锁的基因重复的等位基因变异相关。在这项研究中，我们报告了一个分析的DNA序列变异的两个α-珠蛋白基因重复的鹿小鼠，以确定特定的突变，适应高原缺氧。该研究表明，血红蛋白-氧亲和力的等位基因差异可归因于血红素口袋开口处的五个外部氨基酸残基取代的独立或联合效应。此外，DNA序列变异模式表明，功能不同的α-珠蛋白等位基因是通过有利于不同海拔地区不同基因型的自然选择而维持的。
Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus α-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated α-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity. A major goal in evolutionary biology is to identify the specific genetic mechanisms that have enabled organisms to adapt to their environments. Variation in deer mouse hemoglobin represents an especially promising system for examining the molecular underpinnings of adaptation because it has been possible to establish a mechanistic link between allelic variation in protein function and fitness-related variation in physiological performance. Specifically, adaptive variation in blood biochemistry and aerobic metabolism among mice from different elevations is associated with allelic variation at two closely linked gene duplicates that encode the α-chain subunits of adult hemoglobin. In this study, we report an analysis of DNA sequence variation in the two α-globin gene duplicates of deer mice in order to identify the specific mutations that underlie adaptation to high-altitude hypoxia. The study revealed that allelic differences in hemoglobin-oxygen affinity are attributable to the independent or joint effects of substitutions in five exterior amino acid residues that line the opening of the heme pocket. Additionally, patterns of DNA sequence variation indicate that functionally distinct α-globin alleles are maintained by natural selection that favors different genotypes in different elevational zones.
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DOI：
10.1046/j.1471-8278.2000.00014.x
发表时间：
2001-03-01
期刊：
MOLECULAR ECOLOGY NOTES
影响因子：
--
作者：
Agapow, PM;Burt, A
通讯作者：
Burt, A
DOI：
10.1515/bchm3.1988.369.1.217
发表时间：
1988-04-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
HIEBL, I;WEBER, RE;BRAUNITZER, G
通讯作者：
BRAUNITZER, G
影响因子：
1.5
作者：
Charlesworth, B;Nordborg, M;Charlesworth, D
通讯作者：
Charlesworth, D
影响因子：
2.4
作者：
FERRAND, N
通讯作者：
FERRAND, N
DOI：
10.1107/s0907444994003112
发表时间：
1994-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
BAILEY, S
通讯作者：
BAILEY, S