Co-Variation Approaches to the Evolution of Protein Families

Julien Pele,Madeline Deniaud,Bruck Taddese,Daniel Henrion,Antoine Garnier,Marie Chabbert,Herve Abdi

doi:10.4172/2379-1764.1000250

Abstract

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.

Highlights

Co-variation in amino acid distribution of any two positions in the multiple sequence alignment (MSA) of a protein family is widely used to obtain structural and/or functional information [1]
After mutation of one residue, structural/functional constraints can require a compensatory mutation of another residue to maintain the
The human nonolfactory receptor set includes 283 receptors that can be classified into a dozen of sub-families [19] corresponding to three main evolutionary pathways [20]

Summary

Introduction

Co-variation in amino acid distribution of any two positions in the multiple sequence alignment (MSA) of a protein family is widely used to obtain structural and/or functional information [1]. We compared the different methods structure or to restore the function of the corresponding protein The sets correspond to (1) human non compensatory mutations can depend on direct physical interactions olfactory receptors, (2) receptors characterized by the P2.58 proline between two residues or on an indirect interaction through intermediary pattern (107 members, with 26% sequence identity). The latter receptors residues or a ligand [2]

Methods

Conclusion