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Abstract
BackgroundHeterotachy is the variation in the evolutionary rate of aligned sites in different parts of the phylogenetic tree. It occurs mainly due to epistatic interactions among the substitutions, which are highly complex and make it difficult to study protein evolution. The vast majority of computational evolutionary approaches for studying these epistatic interactions or their evolutionary consequences in proteins require high computational time. However, recently, it has been shown that the evolution of residue solvent accessibility (RSA) is tightly linked with changes in protein fitness and intra-protein epistatic interactions. This provides a computationally fast alternative, based on comparison of evolutionary rates of amino acid replacements with the rates of RSA evolutionary changes in order to recognize any shifts in epistatic interaction.ResultsBased on RSA information, data randomization and phylogenetic approaches, we constructed a software pipeline, which can be used to analyze the evolutionary consequences of intra-protein epistatic interactions with relatively low computational time. We analyzed the evolution of 512 protein families tightly linked to mitochondrial function in Vertebrates and created “mtProtEvol”, the web resource with data on protein evolution. In strict agreement with lifespan and metabolic rate data, we demonstrated that different functional categories of mitochondria-related proteins subjected to selection on accelerated and decelerated RSA rates in rodents and primates. For example, accelerated RSA evolution in rodents has been shown for Krebs cycle enzymes, respiratory chain and reactive oxygen species metabolism, while in primates these functions are stress-response, translation and mtDNA integrity. Decelerated RSA evolution in rodents has been demonstrated for translational machinery and oxidative stress response components.ConclusionsmtProtEvol is an interactive resource focused on evolutionary analysis of epistatic interactions in protein families involved in Vertebrata mitochondria function and available at http://bioinfodbs.kantiana.ru/mtProtEvol/. This resource and the devised software pipeline may be useful tool for researchers in area of protein evolution.
Highlights
Heterotachy is the variation in the evolutionary rate of aligned sites in different parts of the phylogenetic tree
The reasons for considering 20 residue solvent accessibility (RSA) categories as a measure of protein evolution How many categories are enough for evolutionary analysis that is robust to data variation? To answer this question, we analyzed two types of data by random delete-half-jackknifing: amino acid residues classified in 20 classes (20 canonical amino acids or 20 classes of RSA), and amino acid residues classified in 8 classes based on protein
Other important features deposited for each protein family are heterotachy test results obtained by Procov 2.0 [41], results of BLAST screening for sufficient 3D structure homologs in Scratch-1D dataset [42], and various alignment variation features
Summary
Heterotachy is the variation in the evolutionary rate of aligned sites in different parts of the phylogenetic tree. A chance of any amino acid fixation in protein depends on their effect on the structure, function and its interactions with other proteins This results in the observed unevenness in the rates of molecular evolution in different lineages within the same orthologous protein family and in different protein sites in various time intervals. Epistasis leads to coevolution of various protein regions and even different proteins as well as concerted changes [1,2,3,4,5,6,7,8] Another interesting feature of protein evolution that relates to heterotachy is called “fixation bursts” - periods of molecular evolution during which very important processes of fixation of the amino acid substitutions unfold over a relatively short period of time [9]. We decided to uncover such events in evolution of in protein families related to basal cellular functions (e.g. mitochondrial) during the evolution of mammals
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