Hundreds of Genes Experienced Convergent Shifts in Selective Pressure in Marine Mammals

Abstract

Mammal species have made the transition to the marine environment several times, and their lineages represent one of the classical examples of convergent evolution in morphological and physiological traits. Nevertheless, the genetic mechanisms of their phenotypic transition are poorly understood, and investigations into convergence at the molecular level have been inconclusive. While past studies have searched for convergent changes at specific amino acid sites, we propose an alternative strategy to identify those genes that experienced convergent changes in their selective pressures, visible as changes in evolutionary rate specifically in the marine lineages. We present evidence of widespread convergence at the gene level by identifying parallel shifts in evolutionary rate during three independent episodes of mammalian adaptation to the marine environment. Hundreds of genes accelerated their evolutionary rates in all three marine mammal lineages during their transition to aquatic life. These marine-accelerated genes are highly enriched for pathways that control recognized functional adaptations in marine mammals, including muscle physiology, lipid-metabolism, sensory systems, and skin and connective tissue. The accelerations resulted from both adaptive evolution as seen in skin and lung genes, and loss of function as in gustatory and olfactory genes. In regard to sensory systems, this finding provides further evidence that reduced senses of taste and smell are ubiquitous in marine mammals. Our analysis demonstrates the feasibility of identifying genes underlying convergent organism-level characteristics on a genome-wide scale and without prior knowledge of adaptations, and provides a powerful approach for investigating the physiological functions of mammalian genes.

Keywords: adaptive evolution; convergence; convergent evolution; functional constraint; marine mammals; relaxation of constraint.

Fig. 1

Evolutionary rate shifted in a convergent manner for hundreds of genes in marine mammals. (A) Mammals moved from terrestrial to marine environments in 3 independent lineages in this phylogenetic tree of 59 placental mammals. Branches used to infer rate changes associated with the marine phenotype are those leading to the manatee, dolphin, killer whale, Pacific walrus, Weddell seal, and the ancestral branch of the dolphin and killer whale. Other branches represent a set of control branches not expected to show convergence, and which were selected to approximate the topology and branch lengths of the marine set. (B) Gene-by-gene evidence for shifts to faster rates (accelerated) and slower rates (decelerated) associated with the highlighted branches was assessed using a Wilcoxon rank-sum test. The resulting genome-wide distributions for the control branch group show no enrichment of low P values for either acceleration or deceleration. In contrast, the marine branch group exhibited a dramatic shift towards low P values for both faster and slower rates suggesting that the marine environment consistently altered the evolutionary pressures on a large number of genes.

Fig. 2

Representative cases of marine-accelerated and decelerated genes. (A) Relative evolutionary rates of GNAT3, a guanine nucleotide binding protein involved in taste transduction, for 59 placental mammals and their ancestral branches (points in bottom row). Marine branches (large points) had consistently higher rates, resulting in a low probability that the marine rates are the same as the terrestrial species (small points) (P = 8.23 × 10⁻⁵). GNAT3 showed the strongest rate acceleration. This and other taste-related genes provide strong evidence that gustatory senses are reduced or absent in all marine mammals. (B) A compacted view of GNAT3 and other genes with significant marine associations. The background distribution over all non-marine branches is shown as a histogram and the rate values of marine branches are flagged with vertical bars. Other depicted examples are PERP (P = 4.92 × 10⁻⁴), a desmosome component (an epithelial cell-cell junction structure); COL9A2 (P = 2.32 × 10⁻⁴), a cartilage-specific fibril-associated collagen; and XRCC4 (P = 1.53 × 10⁻³), a DNA repair protein with convergently slower rates of evolution in marine mammals.

Fig. 3

Marine-accelerated genes are strongly enriched for interrelated functional categories. Many functions enriched in the top 500 marine-accelerated genes are interconnected through shared genes, as reflected in this network. Each node represents a significantly enriched category with its node diameter proportional to the degree of enrichment (range = 2.3- to 17.7-fold). Displayed categories were restricted to those with enrichment above 2-fold and a FDR q-value below 5%. Edges between nodes reflect shared accelerated genes between categories, and their width is proportional to the degree of sharing (range = 21%–100% shared gene content). The resulting networks group broad biological functions in to olfaction, lung, skin and connective tissue, nervous system, and muscle.