生物学与医学高级技术
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蛋白质家族进化的共变方法

朱利安·贝利、布鲁克·塔德斯、玛德琳·德尼奥、安托万·卡尼尔、丹尼尔·亨利昂、埃尔维·阿布迪和玛丽·查伯特

In a multiple sequence alignment, sequence co-variations result from structural, functional, and/or phylogenetic constraints. Numerous methods have been developed to calculate co-variation scores, but few studies have compared these methods to identify which methods are best suited for the analysis of protein family divergence. Here, we give an overview of widely used methods and identify simple rules for selection of appropriate methods. Specifically, we found that methods such as OMES and ELSC-which favor pairs with intermediate entropy and covariation networks with hub structure-are well suited to reveal evolutionary information on family divergence. When applied to G protein-coupled receptors, these methods support an epistasis model of protein evolution in which, after a key mutation, co-evolution of several residues was necessary to restore and/or shift protein function.