Corrigendum

Abstract

In our most recent update of P450 gene superfamily nomenclature , at least one reader has expressed confusion about the Fig. 1 abscissa labeled "Evolutionary Distance" (d). The erroneous assumption was that the numbers represented millions or billions of years before the present. This is not the case. The scale does not represent linear time. The branchings of distinct genes in this figure represent a combination of orthologous genes in different species and gene duplication events within the same species. Analyses of less complicated P450 phylogenetic trees are presented elsewhere ."Cytochrome P450" is a deceptive name. This term is misleading because it connotes that all P450 gene products are the "same protein" in different tissues and species; this is clearly not the case. Cytochrome P450 is not like, for example, cytochrome c. The functions of different P450 enzymes vary widely (Nebert and Gonzalez, 1987;. Therefore, we expect that the evolutionary constraints on these proteins will also vary widely. One consequence of this is a variation in the evolutionary rate among different P450 genes. This variation is most apparent when branch points representing the same historical divergence event are found at very different evolutionary distances. Two examples are provided to emphasize this point. First, the bacterial P450 sequences diverged from eukaryotic P450 sequences presumably at a fixed point in time, yet there are three prokaryote/eukaryote branch points on the tree, all at very large distances from one another: i.e., d = 1.7 for the CYP55 vs. (CYP105, CYP107) branch point; d = 3.4 for the bacterial cluster plus fungal CYP55 vs. other eukaryotes plus CYP102; and d = 2.1 for the CYP52 and CYP102 families. The second example can be seen with the chicken P450 genes. The CYP2H subfamily and the CYP17 family each branch at d = 0.7-0.9 from other P450 genes. However, the chicken CYP19 branches at d = 0.4, i.e., about one-half that of the other values. Since birds diverged from land animals at a fixed point in time i.e., approximately 320 million years before the present the difference in d suggests that CYP19 is about two times more conserved than the other chicken P450 genes in the tree (Nebert et ai, 1989).In addition to the variation in rate within a single species, there is the further complication of variation between lineages (cf. p. 587 of Nelson and Strobel, 1987). For example, mammals appear to have evolved more rapidly than birds or reptiles. For those who insist on a time scale for P450 evolution, the time scale must therefore be kept

The role of STAT proteins in growth hormone signaling

“…The sexually dimorphic pattern of GH secretion produces distinct dierences in the expression of certain genes. Notable among these are hepatic genes of the cytochrome P450 (CYP) family, particularly those in the gene family CYP2 and CYP3 which encode enzymes involved in the metabolism of endogenous steroids and lipophilic compounds (Nebert, 1991;Waxman et al, 1995). The male-speci®c rat liver P450s include androgen 16a and 2a hydroxylase CYP2C11, the steroid 6b-hydroxylase CYP3A2, testosterone 15a-hydroxylase CYP2A2, and the fatty acid o-hydroxylase CYP4A2.…”

“…The gene encoding hamster CYP 3A10/6b-hydroxylase has been shown to contain a GAS-like element which binds STAT5 in animals exhibiting a male pattern of pulsatile GH release (Subramanian et al, 1995), indicating the presence of a mechanism dependent on the pulsatile GH secretion pattern at the level of gene transcription and STAT5. The female-speci®c steroid sulfate 15b-hydroxylase CYP2C12 is expressed under conditions of continuous GH secretion (Legraverend et al, 1992;Nebert et al, 1991). Both 2C11 and 2C12 are regulated by GH at the transcriptional level (Sundseth et al, 1992).…”

Optimization of yeast‐expressed human liver cytochrome P450 3A4 catalytic activities by coexpressing NADPH‐cytochrome P450 reductase and cytochrome b5

“…The broad substrate specificity is now well understood on the basis of enzyme multiplicity . More than 160 cDNA species coding for P450 have been isolated so far and have been classified on the basis of primary amino acid sequence similarities (Nebert et al, 1991). Although the normal fate of xenobiotic oxidation products is excretion, directly or after further conjugation with a polar group, P450 catalysis sometimes yields highly reactive metabolites that can injure cells by altering macromolecular components, leading especially to carcinogenesis (Kadlubar and Hammons, 1987).…”

Characterization of the cytochrome P‐450IID subfamily in bovine liver

“…With respect to the similarity of amino acid sequences of the subfamily members, the organization of the rat P-450IID subfamily is rather similar to the P-450IIB or P-45OIIC subfamilies. Since some of the members in these subfamilies are moderately similar in amino acid sequence (70-85%; Ged et al, 1988;Romkes et al, 1991 ;Nebert et al, 1991). The members of the P-450IID subfamily in cattle and man change as a subfamily in a concerted fashion (Matsunaga et al, 1990).…”

“…In the P-450IIB and P-45OIIC subfamilies, the multiple members with moderate (70-85%) and high (more than 95%) similarity have been reported (Ged et al, 1988;Nebert et al, 1991). However, it has not been exactly determined how many and what kinds of members are involved in the P-450 subfamily.…”