Differential selection after duplication in mammalian developmental genes
Differential selection after duplication in mammalian developmental genes
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DOI：
10.1093/oxfordjournals.molbev.a003835
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发表时间：
2001-04-01
影响因子：
10.7
通讯作者：
Clark, AG
中科院分区：
文献类型：
--
作者：
Dermitzakis, ET;Clark, AG
基因复制提供了对复制副本的不同功能进行后续改进的机会。通过编码序列的改变或调控区域的改变，重复的拷贝似乎获得了新的或组织特异性的功能。如果这种分化是由自然选择驱动的，我们可以预期，复制的副本会有不同的替代模式。我们使用在人类/小鼠分裂之前复制的基因来验证这一假设，这些基因的同源关系是明确的。原假设是，人类和小鼠之间氨基酸变化的数量在不同的类比中分布相似。我们使用了一种改良的方法来检测这些不同的相似物之间的氨基酸取代模式的异质性。我们的研究结果表明，在人/鼠比较中，许多同源基因对似乎处于差异选择之下。导致多样化的特性似乎在人类和老鼠谱系分裂之前就已经出现了。对分化基因的进一步研究揭示了导致这些基因功能和/或表达差异的氨基酸替代模式。该方法在全基因组数据挖掘中对新发现的基因家族成员的研究以及对重复基因功能进化分歧的不同假设的优点进行比较方面具有实用价值。
Gene duplication provides the opportunity for subsequent refinement of distinct functions of the duplicated copies. Either through changes in coding sequence or changes in regulatory regions, duplicate copies appear to obtain new or tissue-specific functions. If this divergence were driven by natural selection, we would expect duplicated copies to have differentiated patterns of substitutions. We tested this hypothesis using genes that duplicated before the human/mouse split and whose orthologous relations were clear. The null hypothesis is that the number of amino acid changes between humans and mice was distributed similarly across different paralogs. We used a method modified from Tang and Lewontin to detect heterogeneity in the amino acid substitution pattern between those different paralogs. Our results show that many of the paralogous gene pairs appear to be under differential selection in the human/mouse comparison. The properties that led to diversification appear to have arisen before the split of the human and mouse lineages. Further study of the diverged genes revealed insights regarding the patterns of amino acid substitution that resulted in differences in function and/or expression of these genes. This approach has utility in the study of newly identified members of gene families in genomewide data mining and for contrasting the merits of alternative hypotheses for the evolutionary divergence of function of duplicated genes.