Three different sizes of cDNA clones coding for the j31 subunit of human alcohol dehydrogenase (ADH) were isolated from a human cDNA library constructed in bacteriophage Agtll and completely sequenced. Comparisons of these three with two other published ADH X31 cDNA sequences show one silent nucleotide substitution at the third position of colon 220 and two nucleotide differences within the 1337 nucleotides of the 3' untranslated region. Hybridization of a 3' untranslated region of one of the

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... 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 a, 9, and r shows that the subunits a and j3 diverged most recently and that their common ancestor diverged from the ancestor of the subunit r 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 j3 and r are considered to be most recently diverged. The evolutionary rates of nucleotide substitution for the three subunits reveal that the subunit r is evolving with the slowest rate, followed by j9 and a, in that order, implying that the subunit r may be providing the original function of ethanol metabolism.