Interspecies comparison of gene structure and computational analysis of gene regulation of 17beta-hydroxysteroid dehydrogenase type 1.
17Beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) is a key enzyme of 17beta-estradiol biosynthesis, and in rodents is additionally involved in testosterone biosynthesis. The human HSD17B1 gene, located on chromosome 17q12-21, is duplicated in tandem, with the 3'-copy being the functional gene. Here we show by sequencing the gene from a diverse set of related species that this duplication is of very recent evolutionary origin, having occurred in the common ancestor of Hominoidae (apes and humans) while being absent in the closely related Old World monkeys (Macaca) and the outgroup species Tupaia belangeri and Mus musculus. By computational analysis of the conserved regulatory elements in the 5'-untranslated (5'-UTR) and putative promoter region of the HSD17B1 gene and, where present, pseudogene, across our broad sample of species we can show significant differences that might point to the origin of the divergent substrate specificity of human and rodent HSD17B1 and highlight potential functionally relevant differences in regulatory patterns in different evolutionary lineages.
Keller
B
B
GSF-National Research Center for Environment and Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
Ohnesorg
T
T
Mindnich
R
R
Gloeckner
C J
CJ
Breitling
R
R
Scharfe
M
M
Moeller
G
G
Blöcker
H
H
Adamski
J
J
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D020440:Gene Duplication; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics
D020121:5' Untranslated Regions; D004960:Estradiol Dehydrogenases