Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages

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1 Molecular Evolution, Institute for information transmission problems (Kharkevich Institute), Moscow, Russian Federation
2 Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation
3 Skolkovo Institute of Science and Technology, Moscow, Russian Federation
DOI
10.7287/peerj.preprints.3211v2
Published
Accepted
Subject Areas
Evolutionary Studies, Genomics
Keywords
fitness landscape, pathogenic mutations, homoplasy, mitochondria
Copyright
© 2017 Klink et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
Cite this article
Klink GV, Golovin AV, Bazykin GA. 2017. Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages. PeerJ Preprints 5:e3211v2

Abstract

Propensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.

Author Comment

The order of authors is corrected

Supplemental Information

Scripts, raw data and their description

This folder contains my scripts, raw data and a file with their description. I hope this information will help to understand my analysis better if it is needed.

DOI: 10.7287/peerj.preprints.3211v2/supp-1

Supplementary figures and tables

This file contains all supplementary figures and tables mentioned in the manuscript text.

DOI: 10.7287/peerj.preprints.3211v2/supp-2