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

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 (ADGRV1, 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.