DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage
DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage
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DOI：
10.1186/1471-2148-7-191
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发表时间：
2007-10-12
影响因子：
3.4
通讯作者：
Arndt, Peter F.
中科院分区：
文献类型：
--
作者：
de la Chaux, Nicole;Messer, Philipp W.;Arndt, Peter F.
背景：DNA片段（indel）的插入和缺失与替换一起是产生遗传变异的主要突变过程。在这里，我们关注人类基因组蛋白质编码区最近的DNA插入和缺失，以研究蛋白质进化中索引的选择性约束。结果：插入和删除的氨基酸频率与人类蛋白质组的背景氨基酸频率不同。小氨基酸被过度代表，而疏水、脂肪族和芳香氨基酸被强烈抑制。发现indel优先位于不形成重要结构域的蛋白质区域。与其他基因相比，与基本生化反应（如催化活性、连接酶活性、电子传递或分解代谢过程）相关的基因中的氨基酸插入和缺失率较低，因此受到更强的纯化选择。结论：我们的分析表明，人类蛋白质编码区的索引在其对氨基酸序列的结构影响以及它们所处基因的一般特性方面受到不同程度的选择压力。这些发现证实了许多普遍接受的替代选择性约束特征也适用于氨基酸插入和缺失。
Background: Insertions and deletions of DNA segments (indels) are together with substitutions the major mutational processes that generate genetic variation. Here we focus on recent DNA insertions and deletions in protein coding regions of the human genome to investigate selective constraints on indels in protein evolution.Results: Frequencies of inserted and deleted amino acids differ from background amino acid frequencies in the human proteome. Small amino acids are overrepresented, while hydrophobic, aliphatic and aromatic amino acids are strongly suppressed. Indels are found to be preferentially located in protein regions that do not form important structural domains. Amino acid insertion and deletion rates in genes associated with elementary biochemical reactions (e. g. catalytic activity, ligase activity, electron transport, or catabolic process) are lower compared to those in other genes and are therefore subject to stronger purifying selection.Conclusion: Our analysis indicates that indels in human protein coding regions are subject to distinct levels of selective pressure with regard to their structural impact on the amino acid sequence, as well as to general properties of the genes they are located in. These findings confirm that many commonly accepted characteristics of selective constraints for substitutions are also valid for amino acid insertions and deletions.