Evolution of class I alcohol dehydrogenase genes in catarrhine primates: Gene conversion, substitution rates, and gene regulation

Brenda Cheung, Roger S. Holmes, Simon Easteal, Ifor R. Beacham*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    The three class I alcohol dehydrogenases (ADHs) in humans comprise homo- and heterodimers of three subunits (α, β, and γ) 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 βADH subunit is expressed in liven 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 γADH 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 γADH 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 languageEnglish
    Pages (from-to)23-36
    Number of pages14
    JournalMolecular Biology and Evolution
    Volume16
    Issue number1
    DOIs
    Publication statusPublished - Jan 1999

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