Hearing Sensitivity of Primates: Recurrent and Episodic Positive Selection in Hair Cells and Stereocilia Protein-Coding Genes

Abstract

The large spectrum of hearing sensitivity observed in primates results from the impact of environmental and behavioral pressures to optimize sound perception and localization. Although evidence of positive selection in auditory genes has been detected in mammals including in Hominoids, selection has never been investigated in other primates. We analyzed 123 genes highly expressed in the inner ear of 27 primate species and tested to what extent positive selection may have shaped these genes in the order Primates tree. We combined both site and branch-site tests to obtain a comprehensive picture of the positively selected genes (PSGs) involved in hearing sensitivity, and drew a detailed description of the most affected branches in the tree. We chose a conservative approach, and thus focused on confounding factors potentially affecting PSG signals (alignment, GC-biased gene conversion, duplications, heterogeneous sequencing qualities). Using site tests, we showed that around 12% of these genes are PSGs, an α selection value consistent with average human genome estimates (10-15%). Using branch-site tests, we showed that the primate tree is heterogeneously affected by positive selection, with the black snub-nosed monkey, the bushbaby, and the orangutan, being the most impacted branches. A large proportion of these genes is inclined to shape hair cells and stereocilia, which are involved in the mechanotransduction process, known to influence frequency perception. Adaptive selection, and more specifically recurrent adaptive evolution, could have acted in parallel on a set of genes (ADGRVl, USH2A, PCDH15, PTPRQ and ATP8A2) involved in stereocilia growth and the whole complex of bundle links connecting them, in species across different habitats, including high altitude and nocturnal environments.

Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation

“…This suggests that although positive selection likely played a role in the initial evolution of these proteins in vertebrate evolution, they have been evolving primarily neutrally (or near-neutrally) since the divergence of most modern vertebrates. Additionally, although there is evidence of positive selection acting on CDH23 and PCDH15 ( Shen et al 2012 ; Moreira et al 2021 ; Trigila et al 2021 ), the sites identified are not found at the CDH23–PCDH15 interface.…”

The evolutionary tuning of hearing

“…For example, a high-throughput phylogenetic analysis reported that 13% of inner ear expressed genes showed signatures of positive selection in mammals, compared to nonmammalian vertebrates, both in sensory and nonsensory inner ear cells [37]. Moreover, positive selection in inner-ear-expressed genes has also been reported within mammalian branches [38][39][40][41][42][43][44]. In addition, instances of parallel and/or convergent evolution between echolocating bats and whales have been identified in hearing-related genes [38,40,[45][46][47][48][49][50][51], potentially reflecting distinct environmental demands.…”

“…Numerous instances of molecular evolutionary processes have been described for hair bundle proteins (Table 1). Genes encoding proteins constitutive of stereocilia bundles have been described under positive selection in the lineage leading to mammals [37,57], as well as in different mammalian branches (primates [43]; echolocating whales [38,41]; echolocating bats [38]; and mole rats [44,58,59]). These include proteins localised at ankle links and stereocilia rootlets, along the stereocilia shaft, at the stereocilia tips and on the tip links (Figure 2).…”

“…Signatures of positive selection in mammals [43,57] and of parallel evolution in echolocating bats [45,79] have been identified in the coding region of Kcnq4 (Table 2). Moreover, in echolocating bats, positively selected and parallel sites have been identified in Slc4a11 [42], a solute carrier involved in osmotic balance present in the fibroblasts of the spiral ligament and essential for the generation of the endolymphatic potential in the cochlea [80].…”