Parallel Sites Implicate Functional Convergence of the Hearing Gene Prestin among Echolocating Mammals

Abstract

Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/α, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/α and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation.

Molecular parallelism in fast-twitch muscle proteins in echolocating mammals

“…This suggests that the observation of a derived substitution in a background species does not necessarily preclude a functional effect on the protein, and that pure patterns of convergence rarely exists when taxonomic sampling depth increases [38]. Furthermore, in various examples of such as prestin, RNAse1, rhodopsin, Na+/K+-ATPase, functional convergence is observed along with the presence of multiple sites displaying parallel substitutions [14,[39][40][41].…”

“…In order to detect genomic changes involved in the convergent hearing properties of these echolocating lineages, several studies have searched and identified parallel amino acid substitutions in candidate genes with a known hearing-related function such as Dfnb59, Otof, and prestin [9][10][11][12]. Subsequently, in vitro assays demonstrated that parallel substitutions in prestin, a protein known to be critical for high-frequency hearing [13], account for the functional convergence in key parameters of prestin [14]. This shows that searching for molecular parallelism in candidate genes provided insights into the convergent adaptations to high frequency hearing; however, the mechanisms underlying the convergent vocalization aspect of echolocation remain unknown.…”

Detecting the molecular basis of phenotypic convergence

“…Note that Prestin (a.k.a. SLC26A5), known to be involved in echolocation (Li, Liu, Shi, & Zhang, 2010;Liu, Qi, Zhou, Ren, & Shi, 2014;Liu et al, 2010), is the most significant convergent gene out of the 6,332 ones of the dataset. Still for studying echolocation, Shen, Liang, Li, Murphy, and Zhang (2012) screened three genes, namely CDH23, PCDH15 and OTOF, pointing out that "Convergent evolution and expression patterns of OTOF suggest the potential role of nerve and brain in echolocation".…”

Adaptive sequence convergence of the tumor suppressor ADAMTS9 between small-bodied mammals displaying exceptional longevity

“…These studies have highlighted genes that have been repeatedly targeted during the evolution of a given trait. For example, the evolution of echolocation in bats and toothed whales appears to be driven, in part, by common mutations in the genes Prestin [12, 13] and Cdh23 [14, 15]; cardiac glycoside toxin resistance in numerous disparate vertebrates and invertebrates can be explained by identical amino acid substitutions in the enzyme Na+/K+-ATPase [16]; and the repeated convergent evolution of the sodium ion transporter NaV1.7 in hibernating mammals and mole-rats is believed to impart insensitivity to the accumulation of CO2 [17]. These studies, and many others, demonstrate that common selective pressures can drive common mutations in relevant genes.…”