Characterization of the mouse lanosterol 14 alpha-demethylase (CYP51), a new member of the evolutionarily most conserved cytochrome P450 family

Genes encoding sterol 14 alpha-demethylases in eukaryotes and in Mycobacter ium belong to the CYP51 family which is evolutionary the most conserved gen e family within the cytochrome P450 superfamily, We have characterized a ne w member of this family, the mouse lanosterol 14 alpha-demethylase, with th e aim to study the in vivo role of this gene in spermatogenesis in mammals. The amino acid sequence of mouse Cyp51 is 96% identical to rat and 91% to human. Comparison of all known CYP51 proteins by the neighbor-joining metho d suggests that fungal and animal CYP51 genes arose from a common ancestral gene (98.3% probability) and interestingly, that plant and bacterial CYP51 genes share a common progenitor (88.8% probability). This suggests that th e first CYP51 gene may have arisen in eukaryotes and has been transferred h orizontally from plants to Mycobacterium. The mouse CYP51 gene is similar t o 17-kb long and contains 10 exons, Transcription starts at several locatio ns within the CPG island, which is characteristic for the TATA-less houseke eping genes, The mouse 5'-untranslated region (800 bp) contains putative cA MP-responsive elements (CRE), sterol regulatory elements (SRE) and GC-boxes at positions similar to human and rat, suggesting an evolutionary conserve d mechanism of CYP51 transcriptional regulation in mammals. The mouse Cyp51 gene resides on chromosome 5, region A2, close to the centromere. No signa ls outside this region were detected as well as no evidence of processed ps eudogenes using long PCR was found, This indicates that the mouse genome mo st likely lacks CYP51 processed pseudogenes. (C) 2000 Academic Press.