Functional consequences of adaptive evolution of the mammalian a9a10 nicotinic acetylcholine receptor.

M. LIPOVSEK, L. F. FRANCHINI, EDWIN G. PÉREZ, E. KATZ, P. A. FUCHS AND A. B. ELGOYHEN.

Baltimore

Congreso; ARO; 2009

The a9 and a10 nicotinic acetylcholine receptor (nAChR) subunits are expressed in cochlear hair cells, where they form the receptor that participates in the efferent control of auditory function. The nAChR mediates the inhibitory synapse between efferent fibers and outer hair cells in mammals, or short hair cells in birds. The inhibition results from calcium entry through the nAChR, in the presence of acetylcholine (ACh), followed by the activation of a calcium dependent potassium current. Cholinergic efferent feedback to hair cells is a common feature among all vertebrates. Accordingly, we expected that the evolutionary history of the genes coding for the a9 and a10 subunits would be similar throughout the whole Subphylum. However, a detailed analysis of the phylogeny and sequences of these genes showed differences on their evolutionary history along each vertebrate lineage. For example, the a10 subunit from G. gallus is more closely related to mammalian a9 subunits, than to mammalian a10 subunits. Moreover, while a9 subunits are highly conserved among all vertebrates, a10 subunits accumulated a significant amount of changes during the evolution of the mammalian lineage. Sequence analysis of vertebrate CHRNA10 genes show signatures of positive selection in the mammalian lineage, suggesting that the subunits they encode may present different functional properties when comparing mammalian and non-mammalian species (Franchini and Elgoyhen, 2006). Our working hypothesis states that the 910 receptor from R. norvegicus presents functional properties different from those of the G. gallus receptor. In addition, we propose that those differential properties were acquired during the evolution of the mammalian linage, through the positive selection of non-synonymous substitutions.