Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation
Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation
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DOI：
10.1016/s0022-2836(03)00357-7
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发表时间：
2003-05-16
影响因子：
5.6
通讯作者：
Gustafsson, C
中科院分区：
文献类型：
--
作者：
Govindarajan, S;Ness, JE;Gustafsson, C
在蛋白质进化过程中，氨基酸由于功能限制和遗传漂变的结合而发生变化。蛋白质通常含有似乎一起变化的氨基酸对（共变）。对天然存在的直系同源组的共变分析无法区分由蛋白质功能要求保留的残基对和由于沿着共同进化路径的变化而存在的残基对。在这里，我们通过独立重组一组 15 个枯草杆菌蛋白酶直向同源物中的每个天然存在的氨基酸变体，分离了两种类型的共变。我们的分析表明，在这个枯草杆菌蛋白酶直向同源物家族中，几乎所有可能的氨基酸成对组合都可以共存。这表明枯草杆菌蛋白酶直向同源物中发现的氨基酸共变几乎完全是由于变化的共同祖先起源而不是功能限制。我们得出的结论是，天然存在的序列多样性可用于识别可以独立变化而不破坏蛋白质功能的位置。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
During protein evolution, amino acids change due to a combination of functional constraints and genetic drift. Proteins frequently contain pairs of amino acids that appear to change together (covariation). Analysis of covariation from naturally occurring sets of orthologs cannot distinguish between residue pairs retained by functional requirements of the protein and those pairs existing due to changes along a common evolutionary path. Here, we have separated the two types of covariation by independently recombining every naturally occurring amino acid variant within a set of 15 subtilisin orthologs. Our analysis shows that in this family of subtilisin orthologs, almost all possible pairwise combinations of amino acids can coexist. This suggests that amino acid covariation found in the subtilisin orthologs is almost entirely due to common ancestral origin of the changes rather than functional constraints. We conclude that naturally occurring sequence diversity can be used to identify positions that can vary independently without destroying protein function. (C) 2003 Elsevier Science Ltd. All rights reserved.