Аннотация: The dimensionality of complete genome-level fitness landscapes is huge, and studying their shape is hard. Arguably, the most basic level of understanding of a fitness landscape concerns distribution of fitnesses of alleles at a small locus, such as the amino acid propensities at a protein site. In the course of evolution, such single-position landscapes can change due to epistasis (changes elsewhere in the genome) or to environmental fluctuations. Several approaches have been proposed to study the rates and properties of such changes. They can be inferred from a range of patterns, such as changes in direction of selection, patterns of divergence, and phylogenetic distributions of homoplasies. These patterns are informative of the changes of amino acid propensities and, indirectly, of the shape of the fitness landscape. Furthermore, they can be used to distinguish between two major possible causes of changes of site-specific fitness landscapes: epistasis or environmental fluctuations, as these mechanisms predict very different dynamics of site-specific fitness landscapes.

Аннотация: Epistatic interactions between amino acid sites shape the site-specific fitness landscapes, affecting the site-specific probabilities of fixations of different amino acids. There is abundant evidence that epistasis has a major role in shaping the evolution of protein sequences; however, it is hard to quantify its contribution. Here, we reconstruct the phylogeny of several mitochondrial proteins from ~3,000 metazoan species, and use this data to obtain high-resolution site-specific distributions of times between points of occurrence of every amino acid observed at each site. We show that substitutions to the same amino acid are clustered on the phylogenetic tree, and that the extent of clustering is higher in conservative sites. Furthermore, substitutions giving rise to amino acids that segregate as minor frequency alleles in the human population are also phylogenetically clustered near the human branch, showing that much of this polymorphism would be deleterious in other species.