Document Detail

Conservative evolution in duplicated genes of the primate Class I ADH cluster.
MedLine Citation:
PMID:  17204375     Owner:  NLM     Status:  MEDLINE    
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: >90%; introns: >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>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 representing purifying selection. This suggests that purifying selection is more important than gene conversion(s) in maintaining the overall sequence similarity among the Class I genes. We speculate that the highly conserved sequences on the three duplicated genes in primates have been achieved essentially by maintaining stability of the hetero-dimer formation that might have been related to dietary adaptation in primate evolution.
Hiroki Oota; Casey W Dunn; William C Speed; Andrew J Pakstis; Meg A Palmatier; Judith R Kidd; Kenneth K Kidd
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-11-23
Journal Detail:
Title:  Gene     Volume:  392     ISSN:  0378-1119     ISO Abbreviation:  Gene     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-02     Completed Date:  2007-06-18     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  64-76     Citation Subset:  IM    
Department of Genetics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520-8005, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AB243573;  AB243574;  AB243575;  AB243576;  AB243577;  AB243578;  AB243579;  AB243580;  AB243581;  AB243582;  AB243583;  AB243584;  AB243585;  AB243586;  AB243587;  AB243588;  AB243589;  AB243590;  AB243591;  AB243592;  AB243593;  AB243594;  AB243595;  AB243596;  AB243597;  AB243598;  AB243599;  AB243600;  AB243601;  AB243602
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MeSH Terms
Alcohol Dehydrogenase / classification,  genetics*
Base Sequence
Conserved Sequence*
Evolution, Molecular*
Gene Duplication*
Molecular Sequence Data
Primates / genetics*
Sequence Homology, Nucleic Acid
Grant Support
Reg. No./Substance:
EC Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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