Inner Ear Genes Underwent Positive Selection and Adaptation in the Mammalian Lineage

PISCIOTTANO, FRANCISCO; CINALLI, ALEJANDRO R; STOPIELLO, JUAN MATÍAS; CASTAGNA, VALERIA C; ELGOYHEN, ANA BELÉN; RUBINSTEIN, MARCELO; GÓMEZ-CASATI, MARÍA EUGENIA; FRANCHINI, LUCÍA F

MOLECULAR BIOLOGY AND EVOLUTION

OXFORD UNIV PRESS

Año: 2019 vol. 36 p. 1653 - 1670

0737-4038

The mammalian inner ear possesses functional and morphological innovations that contribute to its unique hearingcapacities. The genetic bases underlying the evolution of this mammalian landmark are poorly understood. We proposethat the emergence of morphological and functional innovations in the mammalian inner ear could have been driven byadaptive molecular evolution.In this work, we performed a meta-analysis of available inner ear gene expression data sets in order to identify genes thatshow signatures of adaptive evolution in the mammalian lineage. We analyzed 1,300 inner ear expressed genes andfound that 13% show signatures of positive selection in the mammalian lineage. Several of these genes are known to playan important function in the inner ear. In addition, we identified that a significant proportion of genes showingsignatures of adaptive evolution in mammals have not been previously reported to participate in inner ear developmentand/or physiology.We focused our analysis in two of these genes: STRIP2 and ABLIM2 by generating nullmutantmice andanalyzed their auditory function. We found that mice lacking Strip2 displayed a decrease in neural response amplitudes.In addition, we observed a reduction in the number of afferent synapses, suggesting a potential cochlear neuropathy.Thus, this study shows the usefulness of pursuing a high-throughput evolutionary approach followed by functionalstudies to track down genes that are important for inner ear function.Moreover, this approach sheds light on the geneticbases underlying the evolution of the mammalian inner ear.