Molecular Biology and Evolution, Vol 16, 23-36, Copyright © 1999 by Society for Molecular Biology and Evolution
B Cheung, RS Holmes, S Easteal and IR Beacham
The three class I alcohol dehydrogenases (ADHs) in humans comprise homo-
and heterodimers of three subunits (alpha, beta, and gamma) with greater
than 90% sequence identity. These are encoded by distinct genes (ADH1,
ADH2, and ADH3, respectively) and are all expressed in the liver. In
baboons, only the beta ADH subunit is expressed in liver. A second class I
ADH is expressed in the kidney; we isolated, cloned, and sequenced the cDNA
corresponding to this ADH and conclude that it is of the gamma ADH lineage.
We also amplified and sequenced the 5' noncoding regions of all three class
I baboon ADH genes and the rhesus monkey ADH1 gene and compared their
nucleotide sequences with the corresponding human sequences. There is clear
evidence that the evolution of these genes has been reticulate. At least
three gene conversion events, affecting the coding and 3' noncoding regions
of the genes, are inferred from compatibility and partition matrices and
phylogenetic analysis of the sequences. Our estimation of the evolutionary
history of these genes provides a framework for the investigation of
relative substitution rates and functional variation among the sequences.
Relative-rate tests, designed to account for the reticulate evolution of
these genes, indicate no difference in substitution rate either between
genes encoding different subunits or between human and Old World monkey
lineages. The human and baboon gamma ADH sequences do not show clear
differences at functionally important sites within the coding region, but
they do differ at a number of sites in regions previously proposed to be
regulatory sites for transcriptional control. This variation may explain
the different patterns of gene expression in humans and baboons.
ORIGINAL ARTICLE
Evolution of class I alcohol dehydrogenase genes in catarrhine primates: gene conversion, substitution rates, and gene regulation
School of Biomolecular and Biomedical Science, Griffith University, Queensland, Australia.
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