Evolution of nicotinic acetylcholine receptor subunits

A phylogenetic tree of a gene family of nicotinic acetylcholine receptorsubunits was constructed using 84 nucleotide sequences of receptor subunitsfrom 18 different species in order to elucidate the evolutionary origin ofreceptor subunits. The tree constructed showed that the common ancestor ofall subunits may have appeared first in the nervous system. Moreover, wesuggest that the alpha 1 subunits in the muscle system originated from thecommon ancestor of alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, and beta 3in the nervous system, whereas the beta 1, gamma, delta, and epsilonsubunits in the muscle system shared a common ancestor with the beta 2 andbeta 4 subunits in the nervous system. Using the ratio (f) of the number ofnonsynonymous substitutions to that of synonymous substitutions, wepredicted the functional importance of subunits. We found that the alpha 1and alpha 7 subunits had the lowest f values in the muscle and nervoussystems, respectively, indicating that very strong functional constraintswork on these subunits. This is consistent with the fact that the alpha 1subunit has sites binding to the ligand, and the alpha 7-containingreceptor regulates the release of the transmitter. Moreover, the windowanalysis of the f values showed that strong functional constraints work onthe so-called M2 region in all five types of muscle subunits. Thus, thewindow analysis of the f values is useful for evaluating the degree offunctional constraints in not only the entire gene region, but also thewithin-gene subregion.