Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins

PLoS Genetics. 2021.

Popova A., Neverov A. D.

The mode and rate of evolution of a protein site depends on the effect of its mutations on protein fitness. The fitness effect of a mutation itself can change in the course of evolution for at least two reasons. First, it can be modulated by substitutions occurring at other sites, a phenomenon called epistasis. Second, changes in selection can be non-epistatic, affecting sites independently of one another. Here, we analyse substitutions accumulated by the evolving lineages of the five proteins encoded by the mitochondrial genomes of thousands of species of metazoans and fungi. We show that substitutions at different amino acid sites occur in a coordinated fashion, and this coordination is caused both by epistasis and by episodes of selection affecting groups of sites. We partition each protein into several groups of concordantly evolving sites such that evolution of sites from different groups is discordant, and show that the proteins encoded by the mitochondrial genome consist of coevolving structural blocks. Some of these blocks have a clear functional specialization, e.g. are associated with interfaces between proteins composing respiratory complexes. Together, our results reveal a previously unrecognized complexity in the causes of variation in evolutionary rates between protein sites.

Keywords: coevolution, Mitochondria, Epistasis