Molecular characterization of cDNA clones encoding the human alcohol dehydrogenase .BETA.1 and the evolutionary relationship to the other class I subunits .ALPHA. and .GAMMA..

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Abstract
Three different sizes of cDNA clones coding for the .beta.1 subunit of human alcohol dehydrogenase (ADH) were isolated from a human cDNA library constructed in bacteriophage .lambda.gtll and completely sequenced. Comparisons of these three with two other published ADH .beta.1 cDNA sequences show one silent nucleotide substitution at the third position of codon 220 and two nucleotide differences within the 1337 nucleotides and the 3'' untranslated region. Hybridization of a 3'' untranslated region of one of the .beta.1 cDNA clones to DNAs from various individuals has shown a Rsa I restriction fragment length polymorphism. A phylogenetic tree for class I human ADHs .alpha., .beta., and .gamma. shows that the subunits .alpha. and .beta. diverged most recently and that their common ancestor diverged from the ancestor of the subunit .gamma. earlier. This tree topology differs from that based on equal rates of nucleotide (or amino acid) substitution of the three ADH subunits, in which the subunits .beta. and .gamma. are considered to be most recently diverged. The evolutionary rates of nucleotide substitution for the three subunits reveal that the subunit .gamma. is evolving with the slowest rate, followed by .beta. and .alpha., in that order, implying that the subunit .gamma. may be providing the original function of ethanol metabolism.