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 such variants 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, substitutions giving rise to amino acids that correspond to alleles pathogenic in humans also more frequently occur in 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.
Highlights
Fitness conferred by a particular allele depends on a multitude of factors, both internal to the organism and external to it
We focused on the amino acids observed in the human mitochondrial genome as reference, polymorphic, or pathogenic variants
Using phylogenies reconstructed from two datasets of mitochondrial protein coding genes obtained earlier (Klink & Bazykin, 2017), we asked how homoplasic substitutions giving rise to the human variant are positioned phylogenetically relative to the human branch, compared with other substitutions
Summary
Fitness conferred by a particular allele depends on a multitude of factors, both internal to the organism and external to it. Changes in the propensities for different amino acid residues at a particular protein position, or single-position fitness landscape (SPFL, Bazykin, 2015), have been detected using multiple approaches (Bazykin, 2015; Storz, 2016; Harpak, Bhaskar & Pritchard, 2016). One way to observe such changes is by analyzing how amino acid variants (alleles) and substitutions giving rise to them are distributed over the phylogenetic tree. Multiple substitutions giving rise to the same allele, or homoplasies, are more frequent.
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