Adaptive Evolution in Mammalian Proteins Involved in Cochlear Amplification

ELGOYHEN AB

Baltimore

Congreso; 32nd Midwinter Meeting, Association for Research in Otolaryngology; 2009

The presence of outer hair cells (OHCs) only in the inner ear of mammals and of OHCs active mechanisms, makes the mammalian cochlea a unique hearing device which has the capability of detecting a wide range of frequencies including the highest (more than 100 kHz) in the animal world. Several lines of evidence suggest that the motor protein prestin and á9á10-containing nicotinic receptors (nAChRs) are key players in the function or regulation of OHC active mechanisms. In order to understand how this system evolved in the lineage leading to mammals we performed an evolutionary molecular analysis of these proteins. We calculated the pace of protein evolution as scaled to neutral divergence by the ratio between nonsynonymous (Ka) and synonymous (Ks) substitution rates. Prestin underwent some dramatic changes, especially in the sulphate transporter and antisigma-factor antagonist domain, after the split between mammals and birds. In addition, in placental mammals this gene is under strong purifying selection, suggesting that its function is highly important for these organisms’ fitness and adaptation. On the other hand, the á10 nAChR subunit (but not á9) shows signatures of positive selection along the lineage conducting to mammals. Detailed Ka/Ks window analysis identifies two regions that have undergone accelerated evolution in mammalian a10, part of transmembrane region I and II, two conserved regions among nAChRs. These observations suggest that mammals have evolved not only the motor protein prestin but also a nAChR at the olivocochlear efferent-OHC synapse that is highly tuned to serve its function. Some properties of this receptor might be unique to the mammalian hair cell nAChR and the a10 subunit is the key component underlying its unique properties. Thus, we describe at the molecular level signatures of adaptive evolution of two OHC proteins in the lineage leading to mammals reflecting the importance of these proteins in OHC somatic electromotility.