Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology
ReviewMetazoan cytochrome P450 evolution1
Introduction
There has been considerable growth in the number of cytochrome P450 sequences obtained from plants, animals, lower eukaryotes and bacteria in the last few years. In fact, the nomenclature system devised over 10 years ago [6]is now choked with families and soon the two-digit CYP names will all be assigned. This should not be a problem, since three-digit CYP names will surely suffice for many years. This volume of Comparative Biochemistry and Physiology focuses on animal P450s, so it is fitting to provide an overview of animal P450 evolution, as seen from a wider perspective. Individual animal phyla, subphyla, superclasses and classes will be dealt with in more specialized articles.
Lynn Margulis and Karlene Schwartz, in their book Five Kingdoms [5], recognize 32 animal phyla. We, as humans, tend to think mainly of vertebrates, but that is just one subgroup of the Chordata, which is just one of the 32 phyla of animals. This volume on animal cytochrome P450s has seven phyla represented, Cnidaria (sea anemone), Nematoda (C. elegans), Mollusca, Annelida, Arthropoda (insects, crustaceans) Echinodermata and Chordata (fish, birds, amphibians, reptiles and mammals). This leaves us guessing about the 25 other phyla, but this volume really represents the beginning of a story that will no doubt be epic in nature.
Even with a partial glimpse of animal P450s, much can be learned about the history of this class of proteins. It is instructive to look for the presence or absence of families of P450s in the different groups of organisms to estimate if the families are ancient or modern. Which P450s were present in the ancestors of modern animals, and what do these P450s do? What makes them so useful to a wide variety of creatures? The nomenclature of cytochrome P450s has been published [7], and more recent additions to the collection are maintained at a P450 web site at http://drnelson.utmem.edu/nelsonhomepage.html.
Section snippets
Distribution of P450 families in animals
There are currently 37 cytochrome P450 families identified in the animals. Of these only 16 are found in mammals. The other 21 families are exclusively from insects (six families), molluscs (two families) and the nematode C. elegans (13 families). The 16 families found in mammals are not exclusively mammalian. Table 1 summarizes the distribution of animal P450 families in the various taxa. Many of the mammalian families are also found in birds, fish and other vertebrates. Families 1, 2, 3, 4,
Differences in P450s between major taxonomic groups
The discussion here has emphasized the similarities across taxa. Much can also be learned from the differences between organisms. The C. elegans genome is now 67% complete, so nearly all the P450 families in C. elegans should be present in the sequence databases 3, 9. A comparison of mammals with C. elegans reveals some striking absences. Most notably, the steroidogenic and mitochondrial P450s seem absent in C. elegans. Blast searches of the C. elegans genome database identified 70 P450
The origin of mitochondrial P450s from a microsomal P450
One surprising result of this analysis is the conclusion that mitochondrial P450s did not arrive as part of the ancestral mitochondrial endosymbiont. If mitochondrial P450s did come with the endosymbiont, one would expect to see mitochondrial P450s in nematodes and lower eukaryotes. There are only three P450s in the yeast genome and none are mitochondrial. There do not seem to be any mitochondrial P450s in C. elegans. This implies that mitochondria picked up P450s from outside, presumably by
Recruitment of P450s for expansion in different taxa
The C. elegans P450 complement has three fairly large families, CYP13 (14 members), CYP33 (17 members) and CYP35 (nine members). The CYP13 family belongs to the CYP3 CLAN, but CYP33 and CYP35 cluster together at the top of the tree with CYP1, 2, 18, 17 and 21. During animal development, we have seen the expansion of the CYP2 family in mammals and presumably in other vertebrates, the CYP4 family in insects and now the expansion of CYP3 and another cluster called the C. elegans CLAN, that
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This article was invited by Guest Editors Dr John J. Stegeman and Dr David R. Livingstone to be part of a special issue of CBP on Cytochrome P450 (Comp. Biochem. Physiol. 121 C, pages 1–412, 1998).