Cloning and sequencing of cDNA encoding baboon liver alcohol dehydrogenase: evidence for a common ancestral lineage with the human alcohol dehydrogenase beta subunit and for class I ADH gene duplications predating primate radiation.

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The baboon has at least five alcohol dehydrogenases (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and has distinct liver and kidney class I isozymes. A rat liver class I ADH partial cDNA was used to screen a baboon liver cDNA library. A cDNA clone was isolated and sequenced and found to contain the entire coding region for baboon liver ADH, 12 nucleotides of the 5' noncoding region, and 256 nucleotides of the 3' noncoding region. The amino acid sequence deduced from this cDNA most closely resembles that of human liver ADH beta subunit (ADH-beta): 363 of 374 residues were identical. This suggested that baboon liver class I ADH is of the same ancestral lineage as the human ADH-beta. In contrast to human liver, only a single ADH-beta transcript is observed in baboon liver. A comparison of human and baboon ADH 3' noncoding regions suggests that a single nucleotide change in a polyadenylylation signal consensus sequence may, in part, be responsible for the generation of ADH-beta transcripts with variable-length 3' ends in human liver. A nucleotide substitution rate of 0.5 x 10(-9) substitutions per site per year for primate class I ADH genes was deduced from the data, which suggests that the alpha-beta gamma separation of human ADH genes occurred about 60 million years ago, and that primate class I ADH gene duplications predated primate radiation.