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Conservative evolution in duplicated genes of the primate Class I ADH cluster



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Gene 392 2007 64 76 www elsevier com locate gene Conservative evolution in duplicated genes of the primate Class I ADH cluster Hiroki Oota a Casey W Dunn b 1 William C Speed a Andrew J Pakstis a Meg A Palmatier a Judith R Kidd a Kenneth K Kidd a b b a Department of Genetics Yale University School of Medicine 333 Cedar St New Haven CT USA Department of Ecology and Evolutionary Biology Yale University 165 Prospect St New Haven CT USA Received 19 July 2006 received in revised form 11 November 2006 accepted 15 November 2006 Available online 23 November 2006 Received by J G Zhang Abstract Humans have seven alcohol dehydrogenase genes ADH falling into five classes Three out of the seven genes ADH1A ADH1B and ADH1C belonging to Class I are expressed primarily in liver and code the main enzymes catalyzing ethanol oxidization The three genes are tandemly arrayed within the ADH cluster on chromosome 4 and have very high nucleotide similarity to each other exons N 90 introns N 70 suggesting the genes have been generated by duplication event s One explanation for maintaining similarity of such clustered genes is homogenization via gene conversion s Alternatively recency of the duplications or some other functional constraints might explain the high similarities among the genes To test for gene conversion we sequenced introns 2 3 and 8 of all three Class I genes total N 15 0 kb for five non human primates four great apes and one Old World Monkey OWM and compared them with those of humans The phylogenetic analysis shows each intron sequence clusters strongly within each gene giving no evidence for gene conversion s Several lines of evidence indicate that the first split was between ADH1C and the gene that gave rise to ADH1A and ADH1B We also analyzed cDNA sequences of the three genes that have been previously reported in mouse and Catarrhines OWMs chimpanzee and humans and found that the synonymous and non synonymous substitution dN dS ratios in all pairs are less than 1



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