MoleRate: comparing molecular relative evolutionary rates to detect convergent evolution

In comparative evolutionary genomics, faster or slower evolution of a particular gene, site, or branch in a phylogenetic tree, when compared to the appropriate average, has been interpreted as evidence of conservation, functional importance, or adaptation. With large consortia generating hundreds of genomes, there is an opportunity to interrogate these datasets for evidence of accelerated or reduced evolutionary rates in protein-coding genes associated with the presence or absence of a given phenotype (e.g., marine vs. terrestrial, nocturnal vs. diurnal). Such rate shifts can reflect the molecular basis of convergent phenotypic adaptation when they occur repeatedly across independent lineages. Here, we introduce an explicit phylogenetic rate test, MoleRate, for acceleration or reduction of nucleotide or protein evolutionary rates in focal lineages vs. the rest of the phylogeny. Compared to existing methods, MoleRate offers execution, explicit likelihood-based hypothesis testing, and the ability to detect and filter out potentially aberrant signal from single lineages. We demonstrate MoleRate's performance on simulated and empirical data, and apply it to several mammalian phenotypes. We also highlight its visualization capabilities, which enable exploration and communication of results. These analyses show that MoleRate detects biologically significant enrichments in selective pressure on specific functions related to the given phenotype, and that enrichments in selective pressure related to the given phenotype, absent when random lineages are tested.