Adaptive evolution of a9a10 nicotinic acetylcholine receptors

LIPOVSEK M; FRANCHINI L; KATZ E; FUCHS P; ELGOYHEN AB

Huerta Grande, Córdoba, Argentina

Congreso; II Reunión Conjunta de la SAN y TAN, IIRCN; 2010

Adaptive evolution of a9a10 nicotinic acetylcholine receptors. Marcela Lipovsek, Lucía Franchini, Eleonora Katz, Paul A. Fuchs and Ana Belén Elgoyhen.   The a9a10 nicotinic acetylcholine receptor (a9a10R) mediates efferent inhibition of cochlear hair cells in mammals and birds. This inhibition results from a Ca2+-dependent K+ current activated by Ca2+ entry through a9a10Rs. Using codon-based likelihood models we found evidence of positive selection in the CHRNA10 (Franchini and Elgoyhen, 2006) and CHRNA9 genes within the mammalian lineage. We propose that, as a result of non-synonymous substitutions, mammalian and non-mammalian a9a10Rs should present differential functional properties. To test this hypothesis, we studied mammalian (rat) and avian (chicken) a9a10Rs expressed in Xenopus oocytes. We found that these evolution-driven modifications dramatically changed the receptor’s properties when comparing rat to chicken. Unlike rat, chicken a10 subunits formed a functional receptor. Strikingly, the Ca2+ permeability of the avian a9a10Rs was substantially lower than that of its mammalian counterpart. Moreover, aminoacid substitutions in the a9 subunit (and not a10) were responsible for the encountered differences in Ca2+ permeability. These results indicate a different evolutionary history of mammalian versus non-mammalian a9a10Rs, with important functional implications for the operation of the efferent system in each species.