Abstract
Amino acid propensities at amino acid sites change with time due to epistatic interactions or changing environment, affecting the probabilities of fixation of different amino acids. Such changes should lead to an increased rate of homoplasies (reversals, parallelisms, and convergences) at closely related species. Here, we reconstruct the phylogeny of twelve mitochondrial proteins from several thousand metazoan species, and measure the phylogenetic distances between branches at which either the same allele originated repeatedly due to homoplasies, or different alleles originated due to divergent substitutions. The mean phylogenetic distance between parallel substitutions is ∼20% lower than the mean phylogenetic distance between divergent substitutions, indicating that a variant fixed in a species is more likely to be deleterious in a more phylogenetically remote species, compared with a more closely related species. These findings are robust to artefacts of phylogenetic reconstruction or of pooling of sites from different conservation classes or functional groups, and imply that single-position fitness landscapes change at rates similar to rates of amino acid changes.