Adaptive Evolution of Mammalian Proteins Involved in cochlear amplification

ELGOYHEN AB

Congreso; 8th Molecular Biology of Hearing and Deafness; 2011

Adaptive Evolution of Mammalian Proteins Involved in Cochlear Amplification   Ana Belén Elgoyhen, INGEBI-CONICET, Buenos Aires, Argentina  The remarkable high-frequency sensitivity and selectivity of the mammalian auditory system has been attributed to the evolution of mechanical amplification. Somatic electromotility in cochlear outer hair cells, as the basis for cochlear amplification, is a mammalian novelty and is largely dependent upon rapid cell length changes proposed to be mediated by the motor-protein prestin, a member of the solute carrier anion-transport family 26. Using codon-based likelihood models we have shown evidences for positive selection in the motor-protein prestin only in the mammalian lineage, supporting the hypothesis that lineage-specific adaptation-driven molecular changes endowed prestin with the ability to mediate somatic electromotility (Franchini and Elgoyhen 2006). Moreover, signatures of positive selection were also observed for the mammalian a10, but not the a9, nicotinic cholinergic receptor subunits. Since the a9a10 nicotinic cholinergic receptor mediates inhibitory olivocochlear efferent effects on hair cells across vertebrates, these results suggest that evolution-driven modifications of the a10 subunit probably allowed the a9a10 heteromeric receptor to serve a differential function in the mammalian cochlea. We have now analyzed the functional properties of a mammalian a9a10 receptor (rat) and compared them to those of a non-mammalian vertebrate species (chicken). We show that whereas rat receptors have a remarkably high Ca2+ permeability (PCa/PNa 9), chicken receptors have a low permeability ratio (< 2). These results will be discussed on the basis of the function of this nicotinic receptor on the efferent-hair cell synapse