Widespread evolutionary crosstalk among protein domains in the context of multi-domain proteins.

David Jakubec,Jiří Vymĕtal,Jiří Vondrášek,Miroslav Kratochvíl

doi:10.1371/journal.pone.0203085

Abstract

Domains are distinct units within proteins that typically can fold independently into recognizable three-dimensional structures to facilitate their functions. The structural and functional independence of protein domains is reflected by their apparent modularity in the context of multi-domain proteins. In this work, we examined the coupling of evolution of domain sequences co-occurring within multi-domain proteins to see if it proceeds independently, or in a coordinated manner. We used continuous information theory measures to assess the extent of correlated mutations among domains in multi-domain proteins from organisms across the tree of life. In all multi-domain architectures we examined, domains co-occurring within protein sequences had to some degree undergone concerted evolution. This finding challenges the notion of complete modularity and independence of protein domains, providing new perspective on the evolution of protein sequence and function.

Highlights

Domains are basic functional and structural elements of proteins
The modular nature of domains arises from their ability to adopt well-defined threedimensional (3D) structures (Fig 1A) that often facilitate their functions independently of their sequential surroundings. [1,2,3] Most eukaryotic proteins contain multiple domains [4, 5], and interactions among these domains can mediate allosteric regulation [6] or give rise to novel domain functions different from those found in isolation or other domain arrangements
Structural changes driven by mutations in the primary sequence are one mechanism underlying the acquisition of novel domain functions. [4, 7, 8] Structural and functional constraints often require that evolution be coordinated between groups of amino acid residues in proteins (Fig 1B). [9,10,11] Covariation in amino acid composition between positions in multiple sequence alignments (MSAs) can be indicative of physical interactions between the residues

Summary

Introduction

In addition to sequence mutations, protein evolution is driven by combining existing domains into novel arrangements. [1,2,3] Most eukaryotic proteins contain multiple domains [4, 5], and interactions among these domains can mediate allosteric regulation [6] or give rise to novel domain functions different from those found in isolation or other domain arrangements. Structural changes driven by mutations in the primary sequence are one mechanism underlying the acquisition of novel domain functions. [4, 7, 8] Structural and functional constraints often require that evolution be coordinated between groups of amino acid residues in proteins (Fig 1B). [9,10,11] Covariation in amino acid composition between positions in multiple sequence alignments (MSAs) can be indicative of physical interactions between the residues. Structural changes driven by mutations in the primary sequence are one mechanism underlying the acquisition of novel domain functions. [4, 7, 8] Structural and functional constraints often require that evolution be coordinated between groups of amino acid residues in proteins (Fig 1B). [9,10,11] Covariation in amino acid composition between positions in multiple sequence alignments (MSAs) can be indicative of physical interactions between the residues

Methods

Results

Discussion

Conclusion