tailieunhanh - Báo cáo Y học: Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial arti®cial chromosomes

Mammalian alcohol dehydrogenases (ADH) 3 form a com-plex enzyme system based on amino-acid sequence, func-tional properties, and gene expression pattern. At least four mouseAdhgenes are known to encode di erent enzyme classes that share less than 60% amino-acid sequence iden-tity. Two ADH-containing and overlapping C57BL/6 bacterial arti®cial chromosome clones, RP23-393J8 and -463H24, were identi®ed in a library screen, physically mapped, and sequenced. | Eur. J. Biochem. 269 224-232 2002 FEBS 2002 Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes Gabor Szalai1 Greaa Duester2. Robert Friedman1 Honaaui Jia3 ShaoPina Lin3. Bruce A Roe3 B B B B B Bl and Michael Ri Felder1 1Department of Biological Sciences University of South Carolina Columbia USA 2Gene Regulation Program The Burnham Institute La Jolla CA USA 3Department of Chemistry and Biochemistry University of Oklahoma Norman OK USA Mammalian alcohol dehydrogenases ADH form a complex enzyme system based on amino-acid sequence functional properties and gene expression pattern. At least four mouse Adh genes are known to encode different enzyme classes that share less than 60 amino-acid sequence identity. Two ADH-containing and overlapping C57BL 6 bacterial artifcial chromosome clones RP23-393J8 and -463H24 were identified in a library screen physically mapped and sequenced. The gene order in the complex and two new mouse genes Adh5a and Adh5b and a pseudogene Adh5ps were obtained from the physical map and sequence. The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I-V the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene. Keywords alcohol dehydrogenase mouse gene complex. The alcohol dehydrogenases ADHs EC are zinc-containing dimeric enzymes found in the cytosolic fraction of the cell that are capable of reversible oxidation of a spectrum of primary and secondary alcohols to the corresponding aldehydes and ketones. Mammalian ADHs currently known are grouped into six distinct classes 1-3 with members of different classes sharing less .