Positive and strongly relaxed purifying selection drive the evolution of repeats in proteins.

Erez Persi,Yuri I Wolf,Eugene V Koonin

doi:10.1038/ncomms13570

Abstract

Protein repeats are considered hotspots of protein evolution, associated with acquisition of new functions and novel phenotypic traits, including disease. Paradoxically, however, repeats are often strongly conserved through long spans of evolution. To resolve this conundrum, it is necessary to directly compare paralogous (horizontal) evolution of repeats within proteins with their orthologous (vertical) evolution through speciation. Here we develop a rigorous methodology to identify highly periodic repeats with significant sequence similarity, for which evolutionary rates and selection (dN/dS) can be estimated, and systematically characterize their evolution. We show that horizontal evolution of repeats is markedly accelerated compared with their divergence from orthologues in closely related species. This observation is universal across the diversity of life forms and implies a biphasic evolutionary regime whereby new copies experience rapid functional divergence under combined effects of strongly relaxed purifying selection and positive selection, followed by fixation and conservation of each individual repeat.

Highlights

Protein repeats are considered hotspots of protein evolution, associated with acquisition of new functions and novel phenotypic traits, including disease
Repeats in protein-coding genes are often viewed as a major source of new raw genetic material, which rapidly evolves and facilitates the acquisition of new functions and complex phenotypic traits[22,23,24,25,26,52]
A new copy is assumed to be free of selective constraints, such that a new function can emerge rapidly, minimizing the risk of deleterious effects

Summary

Introduction

Protein repeats are considered hotspots of protein evolution, associated with acquisition of new functions and novel phenotypic traits, including disease. We show that horizontal evolution of repeats is markedly accelerated compared with their divergence from orthologues in closely related species This observation is universal across the diversity of life forms and implies a biphasic evolutionary regime whereby new copies experience rapid functional divergence under combined effects of strongly relaxed purifying selection and positive selection, followed by fixation and conservation of each individual repeat. There seems to be a conundrum between the overall evolutionary conservation in repetitive regions of proteins and rapid change of repeats associated with a variety of biological processes We resolve this apparent contradiction by revealing a dramatic difference between the regimes of intra-protein (horizontal) evolution of repeats and inter-protein (vertical) evolution of repeats in orthologous proteins

Methods

Results

Conclusion