Molecular Biology and Evolution, Vol 15, 518-527, Copyright © 1998 by Society for Molecular Biology and Evolution
K Tsunoyama and T Gojobori
A phylogenetic tree of a gene family of nicotinic acetylcholine receptor
subunits was constructed using 84 nucleotide sequences of receptor subunits
from 18 different species in order to elucidate the evolutionary origin of
receptor subunits. The tree constructed showed that the common ancestor of
all subunits may have appeared first in the nervous system. Moreover, we
suggest that the alpha 1 subunits in the muscle system originated from the
common ancestor of alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, and beta 3
in the nervous system, whereas the beta 1, gamma, delta, and epsilon
subunits in the muscle system shared a common ancestor with the beta 2 and
beta 4 subunits in the nervous system. Using the ratio (f) of the number of
nonsynonymous substitutions to that of synonymous substitutions, we
predicted the functional importance of subunits. We found that the alpha 1
and alpha 7 subunits had the lowest f values in the muscle and nervous
systems, respectively, indicating that very strong functional constraints
work on these subunits. This is consistent with the fact that the alpha 1
subunit has sites binding to the ligand, and the alpha 7-containing
receptor regulates the release of the transmitter. Moreover, the window
analysis of the f values showed that strong functional constraints work on
the so-called M2 region in all five types of muscle subunits. Thus, the
window analysis of the f values is useful for evaluating the degree of
functional constraints in not only the entire gene region, but also the
within-gene subregion.
ORIGINAL ARTICLE
Evolution of nicotinic acetylcholine receptor subunits
Department of Genetics, Graduate University for Advanced Studies, Mishima, Japan.
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