Zheng Ying, Xu Dongping, Gu Xun
Department of Genetics, Development & Cell Biology, Center for Bioinformatics and Biological Statistics, Iowa State University, Iowa 50011, USA.
J Exp Zool B Mol Dev Evol. 2007 Jan 15;308(1):85-96. doi: 10.1002/jez.b.21140.
In this article, we use animal G-protein alpha subunit family as an example to illustrate a comprehensive analytical pipeline for detecting different types of functional divergence of protein families, which is phylogeny-dependent, combined with ancestral sequence inference and available protein structure information. In particular, we focus on (i) Type-I functional divergence, or site-specific rate shift, as typically exemplified by amino acid residue highly conserved in a subset of homologous genes but highly variable in a different subset of homologous genes, and (ii) Type-II functional divergence, or the shift of cluster-specific amino acid property, as exemplified by a radical shift of amino acid property between duplicate genes, which is otherwise evolutionally conserved. We utilized the software DIVERGE2 to carry out these analyses. In the case of G-protein alpha subunit gene family, we have predicted amino acid residues that are related to either Type-I or Type-II functional divergence. The inferred ancestral sequences for these sites are helpful to explore the trends of functional divergence. Finally, these predicted residues are mapped to the protein structures to test whether these residues may have 3D structure or solvent accessibility preference.
在本文中，我们以动物G蛋白α亚基家族为例，阐述一种用于检测蛋白质家族不同类型功能分化的综合分析流程，该流程依赖系统发育，并结合了祖先序列推断和可用的蛋白质结构信息。具体而言，我们关注：（i）I型功能分化，即位点特异性速率变化，典型例子是在一部分同源基因中高度保守但在另一部分同源基因中高度可变的氨基酸残基；（ii）II型功能分化，即簇特异性氨基酸性质的变化，例如重复基因之间氨基酸性质的剧烈变化，而在其他方面是进化保守的。我们利用DIVERGE2软件进行这些分析。对于G蛋白α亚基基因家族，我们预测了与I型或II型功能分化相关的氨基酸残基。这些位点的推断祖先序列有助于探索功能分化的趋势。最后，将这些预测的残基映射到蛋白质结构上，以测试这些残基是否可能具有三维结构或溶剂可及性偏好。
