Substitutions into amino acids that are pathogenic in human mitochondrial proteins are more frequent in lineages closely related to human than in distant lineages

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 niitochondrial genes, and analyze their occurrence in non-hunian 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, i substitutions giving rise to amino acids that correspond to alleles pathogenic n humans also more frequently occur in more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable n human mitochondria than a variant that may only be fit after a substantial perturbation or tne protein structure.