Review
Arthropod CYPomes illustrate the tempo and mode in P450 evolution

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Abstract

The great diversity of P450 genes in a variety of organisms is well documented but not well explained. The number of CYP genes in each species is highly variable and this is shown here for arthropod, mainly insect CYPomes. Pairs of recognizable orthologs are but a small portion of the CYPome, but species- or lineage-specific expansions of CYP subfamilies are consistently observed. These “blooms” of CYP genes have their origin in multiple gene duplications, although some subfamilies expand and others do not. Stochastic birth and death models of CYP gene proliferation are sufficient to explain blooms, and speciation events may play important roles in CYPome diversity between lineages. Mitochondrial clan P450s are a monophyletic group of genes that has seen several blooms in insects, but apparently not in vertebrates.

Introduction

The P450 gene superfamily is large enough that after transcriptome and proteome became the logical followers of genome in the biological discourse, the term CYPome was introduced in the literature [1]. As this issue is dedicated to Klaus Ruckpaul and his contributions to the P450 field, it seems appropriate to celebrate by joining in the use of this evocative term. The explosion of new knowledge on CYPomes brought about by the sequencing of various genomes is impacting the field of P450 research in many ways. The sheer number of P450 genes, the size of the CYPomes, is baffling (Nelson, this issue). Humans have a CYPome of 57 P450 genes and 58 pseudogenes, distributed in 18 CYP families, but the mouse has a CYPome of 102 P450 genes and nearly 90 pseudogenes. The human CYP2D6 “debrisoquine hydroxylase” gene has nine CYP2D paralogs in the mouse [2]. The number of P450 genes is therefore highly variable over evolutionary time, even over the very short 90 million years (MY) that separate human and mouse.

This highly dynamic nature of the P450 superfamily shown by the difference between humans and mouse is neither just curious nor just obvious. Beyond the implications of P450 diversity for our reliance on “model” species in research, particularly risk assessment in toxicology, the origins of P450 diversity are of great interest intrinsically. Because it is so large, the P450 superfamily can serve as a model for gene family evolution, perhaps one where knowledge of specific functions of P450 can bring deeper insights into the mechanism of gene family evolution. Therefore, while it is certainly presumptuous to paraphrase the title of G. G. Simpson's famous book on evolution for this paper, both the tempo (rates) and the mode (patterns and mechanisms) of evolution of the CYPomes are fascinating and still poorly understood.

Here, I will examine the dynamics of P450 evolution in the light of current concepts of gene family evolution. I will first describe the diversity of CYPomes using arthropods (mainly insects) as examples, then attempt to describe how the processes of gene duplications in the P450 family have shaped its diversity. I close with a discussion of mitochondrial P450 that are surprisingly diverse in their own right, with insects and vertebrates having found different ways to metabolize xenobiotics within this organelle.

Section snippets

P450 diversity in arthropods

By all estimates, the number of arthropod species and of insects in particular is larger than that of other animals, fungi and plants combined. Coleoptera (beetles) and Lepidoptera (moths and butterflies) together make up more than half of all insect species [3]. The diversity of P450 genes in arthropods has been documented gradually over the last 10 years, with an increasing number of genomes available for study. This rich dataset allows us to study the patterns of evolution of the P450

CYPome diversity: Past and present

In the theoretical scheme shown in Fig. 4, the diversity of CYP families in a typical organism is represented over evolutionary time. In this scheme, many will recognize the typical way that the fossil record is illustrated. The vertical axis represents time, an arrow pointing up to the present, and the horizontal axis represents diversity, such as the prevalence of a certain type of fossil at a particular time in the past. Typically, each group of fossils or clade is represented by an

Neofunctionalization and subfunctionalization

The fate of duplicated genes has been extensively studied [21]. Although one would assume that duplicated genes are initially identical and redundant, this is rarely exactly true (size of the duplicated segment, position effect, allelic sampling) [36] so that the two members of a duplicated pair do not have formally the same probability to have the same fate. However, it is statistically very difficult to detect asymmetric rates of duplicate gene divergence [36]. Gene death

Mitochondrial P450s

It is somewhat paradoxical that during the early historical development of P450 research until the late 1970s, the number of mammalian mitochondrial P450s involved in specific physiological functions was greater than that of microsomal xenobiotic metabolizing P450s (the “3MC-inducible” and “phenobarbital-inducible” types). This view of P450 diversity has changed dramatically, but the idea that mitochondrial P450s are restricted to specific physiological or endocrine functions is still widely

References (75)

  • J.E. Galagan et al.

    RIP: the evolutionary cost of genome defense

    Trends Genet

    (2004)
  • M. Lynch et al.

    The altered evolutionary trajectories of gene duplicates

    Trends Genet

    (2004)
  • M.H. Heim et al.

    Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6

    Genomics

    (1992)
  • D. Rozman et al.

    The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family

    Arch Biochem Biophys

    (1996)
  • T. Sztal et al.

    Two independent duplications forming the Cyp307a genes in Drosophila

    Insect Biochem Mol Biol

    (2007)
  • O. Gotoh

    Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences

    J Biol Chem

    (1992)
  • N. Takaya et al.

    Cytochrome p450nor, a novel class of mitochondrial cytochrome P450 involved in nitrate respiration in the fungus Fusarium oxysporum

    Arch Biochem Biophys

    (1999)
  • F.P. Guengerich et al.

    Function of human cytochrome P450s: characterization of the orphans

    Biochem Biophys Res Comm

    (2005)
  • B.O. Lund et al.

    Novel involvement of a mitochondrial steroid hydroxylase (P450c11) in xenobiotic metabolism

    J Biol Chem

    (1995)
  • V.M. Guzov et al.

    CYP12A1, a mitochondrial cytochrome P450 from the house fly

    Arch Biochem Biophys

    (1998)
  • P.J. Daborn et al.

    Evaluating the insecticide resistance potential of eight Drosophila melanogaster cytochrome P450 genes by transgenic over-expression

    Insect Biochem Mol Biol

    (2007)
  • R. Menzel et al.

    A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible

    Arch Biochem Biophys

    (2001)
  • F. Hannemann et al.

    Cytochrome P450 systems—biological variations of electron transport chains

    Biochim Biophys Acta

    (2007)
  • D.R. Nelson

    Cytochrome P450 and the individuality of species

    Arch Biochem Biophys

    (1999)
  • C.M. Jenkins et al.

    Flavodoxin and NADPH-flavodoxin reductase from Escherichia coli support bovine cytochromeP450c17 hydroxylase activities

    J Biol Chem

    (1994)
  • H.K. Anandatheerthavarada et al.

    Localization of multiple forms of inducible cytochromes P450 in rat liver mitochondria: immunological characteristics and patterns of xenobiotic substrate metabolism

    Arch Biochem Biophys

    (1997)
  • M.B. Genter et al.

    Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment

    Biochem Biophys Res Commun

    (2006)
  • M. Seliskar et al.

    Mammalian cytochromes P450—importance of tissue specificity

    Biochim Biophys Acta

    (2007)
  • I.A. Pikuleva et al.

    An additional electrostatic interaction between adrenodoxin and P450c27(CYP27A1) results in tighter binding than between adrenodoxin and P450scc (CYP11A1)

    J Biol Chem

    (1999)
  • D.R. Nelson et al.

    Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants

    Pharmacogenetics

    (2004)
  • D. Grimaldi et al.

    Evolution of the Insects

    (2005)
  • R. Feyereisen

    Evolution of insect P450

    Biochem Soc Trans

    (2006)
  • J.J. Emerson et al.

    Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster

    Science

    (2008)
  • P.J. Daborn et al.

    A single P450 allele associated with insecticide resistance in Drosophila

    Science

    (2002)
  • H. Ranson et al.

    Evolution of supergene families associated with insecticide resistance

    Science

    (2002)
  • C. Helvig et al.

    CYP15A1, the cytochrome P450 that catalyzes epoxidation of methyl farnesoate to Juvenile Hormone III in cockroach corpora allata

    Proc Natl Acad Sci USA

    (2004)
  • C. Claudianos et al.

    A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee

    Insect Mol Biol

    (2006)
  • Cited by (0)

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