Structural and evolutionary studies on sterol 14-demethylase P450 (CYP51), the most conserved P450 monooxygenase: II. Evolutionary analysis of protein and gene structures.
Phylogenetic analyses based on protein sequence data indicated that sterol 14-demethylase P450 (CYP51) and bacterial CYP51-like protein were joined into a distinctive evolutionary cluster, CYP51 cluster, within the CYP protein superfamily. The most probable branch topology of the CYP51 phylogenetic tree was (bacteria, (plants, (fungi, mammals))), which is comparable to the phylogeny of major kingdoms of living matter, suggesting that CYP51 has been conserved from the era of prokaryotic evolution. This may be strong evidence supporting the prokaryotic origin of P450. Structure of flanking regions and the number and insertion sites of introns are quite different between mammalian and fungal CYP51s. This fact indicates that different mechanisms are operative in evolution of protein sequences and gene structures. CYP51 is the first example violating the well-documented rule that the basic structure of a gene, including intron insertion sites, is well conserved in each P450 family. One CYP51 processed a pseudogene was found in rat genome. Nonsynonymous nucleotide divergence observed between the pseudogene and CYP51 cDNA was less than one-fifth of the synonymous divergence. This unusually low rate of nonsynonymous nucleotide changes in the pseudogene suggests that it may be derived from another CYP51, which might have been active for a significant duration in the past.
Yoshida
Y
Y
School of Pharmaceutical Sciences and Interdisciplinary Research Institute for Biosciences, Mukogawa Women's University, Nishinomiya. yoshiday@mwu.mukogawa-u.ac.jp
Noshiro
M
M
Aoyama
Y
Y
Kawamoto
T
T
Horiuchi
T
T
Gotoh
O
O
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D066298:In Vitro Techniques; D007438:Introns; D008969:Molecular Sequence Data; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011544:Pseudogenes; D051381:Rats; D017386:Sequence Homology, Amino Acid; D058886:Sterol 14-Demethylase; D013261:Sterols / Q000096:biosynthesis
D001426:Bacterial Proteins; C548418:CYP51A1 protein, human; C548417:Cyp51 protein, rat; D013261:Sterols; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase