A functional enrichment test for molecular convergent evolution finds a clear protein-coding signal in echolocating bats and whales

Abstract

Distantly related species entering similar biological niches often adapt by evolving similar morphological and physiological characters. How much genomic molecular convergence (particularly of highly constrained coding sequence) contributes to convergent phenotypic evolution, such as echolocation in bats and whales, is a long-standing fundamental question. Like others, we find that convergent amino acid substitutions are not more abundant in echolocating mammals compared to their outgroups. However, we also ask a more informative question about the genomic distribution of convergent substitutions by devising a test to determine which, if any, of more than 4,000 tissue-affecting gene sets is most statistically enriched with convergent substitutions. We find that the gene set most overrepresented (q-value = 2.2e-3) with convergent substitutions in echolocators, affecting 18 genes, regulates development of the cochlear ganglion, a structure with empirically supported relevance to echolocation. Conversely, when comparing to nonecholocating outgroups, no significant gene set enrichment exists. For aquatic and high-altitude mammals, our analysis highlights 15 and 16 genes from the gene sets most affected by molecular convergence which regulate skin and lung physiology, respectively. Importantly, our test requires that the most convergence-enriched set cannot also be enriched for divergent substitutions, such as in the pattern produced by inactivated vision genes in subterranean mammals. Showing a clear role for adaptive protein-coding molecular convergence, we discover nearly 2,600 convergent positions, highlight 77 of them in 3 organs, and provide code to investigate other clades across the tree of life.

Comparative genomics provides insights into the aquatic adaptations of mammals

“…Cetaceans have many unique biological characteristics, including echolocation, deep diving, and large variation in body size. The molecular basis of echolocation has been well studied previously ( 32 – 34 ). However, based on more comprehensive data, we systematically reanalyzed the 504 hearing-related gene sequences in 40 species, including two groups of echolocating bats (group M: big brown bat, Natal long-fingered bat, Brandt’s bat, and little brown bat and group G: greater horseshoe bat) and 16 toothed whales (group T) ( SI Appendix , Fig.…”

A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals

“…In each species, for every gene to which an orthologous chain was assigned, we used the alignments derived from the chain to determine the orthologous amino acid sequence for every transcript of that gene. Because exon boundaries sometimes shift for evolutionary or alignment reasons, we excluded the first and last two amino acid positions in each exon for all downstream analyses ( 23 ). Gaps in chain alignments found in regions containing an assembly gap in the query species were masked out to avoid confusing them with true deletions in the query genome.…”

Novel regulators of growth identified in the evolution of fin proportion in flying fish

“…This low probability makes parallel genetic changes strong candidates for association with specific phenotypes when they occur in lineages with independently-derived character changes [44]. Importantly, while the number of convergent substitutions across species with convergently evolved traits is frequently similar to control comparisons lacking known trait convergence [45,46], a recent analysis of multiple instances of molecular convergences in mammals indicates that convergent amino acid substitutions are not randomly distributed in the genome and are likely associated with genes related to key phenotypic traits [47]. Regardless of frequency, parallel amino acid changes are thus compelling candidates for functional association with convergent evolutionary traits.…”