Abstract

Protein-coding genes evolve at different rates, and the influence of different parameters, from gene size to expression level, has been extensively studied. While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals. Here we investigate these relations further, especially taking in account gene expression in different organs as well as indirect correlations between parameters. We used RNA-seq data from two large datasets, covering 22 mouse tissues and 27 human tissues. Over all tissues, evolutionary rate only correlates weakly with levels and breadth of expression. The strongest explanatory factors of purifying selection are GC content, expression in many developmental stages, and expression in brain tissues. While the main component of evolutionary rate is purifying selection, we also find tissue-specific patterns for sites under neutral evolution and for positive selection. We observe fast evolution of genes expressed in testis, but also in other tissues, notably liver, which are explained by weak purifying selection rather than by positive selection.

Highlights

  • Understanding the causes of variation in protein sequence evolutionary rates is one of the major aims of molecular evolution, and has even been called a "quest for the universals of protein evolution" [1]

  • While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals

  • While the main component of evolutionary rate is purifying selection, we find tissue-specific patterns for sites under neutral evolution and for positive selection

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Summary

Introduction

Understanding the causes of variation in protein sequence evolutionary rates is one of the major aims of molecular evolution, and has even been called a "quest for the universals of protein evolution" [1]. Expression level has been shown to be the best predictor of evolutionary rate in yeasts and bacteria: highly expressed proteins are generally more conserved [4,5,6]. It has been suggested that selection against protein misfolding is sufficient to explain covariation of gene expression and evolutionary rate across taxa, including mouse and human [14]. This notably explains the slower evolution of brain-expressed genes; the relation with the influence of breadth of PLOS ONE | DOI:10.1371/journal.pone.0131673. This notably explains the slower evolution of brain-expressed genes; the relation with the influence of breadth of PLOS ONE | DOI:10.1371/journal.pone.0131673 June 29, 2015

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