The cytochrome P450 genesis locus: the origin and evolution of animal cytochrome P450s

The neighbourhoods of cytochrome P450 (CYP) genes in deuterostome genomes, as well as those of the cnidarians Nematostella vectensis and Acropora digitifera and the placozoan Trichoplax adhaerens were examined to find clues concerning the evolution of CYP genes in animals. CYP genes created by the 2R whole genome duplications in chordates have been identified. Both microsynteny and macrosynteny were used to identify genes that coexisted near CYP genes in the animal ancestor. We show that all 11 CYP clans began in a common gene environment. The evidence implies the existence of a single locus, which we term the ‘cytochrome P450 genesis locus’, where one progenitor CYP gene duplicated to create a tandem set of genes that were precursors of the 11 animal CYP clans: CYP Clans 2, 3, 4, 7, 19, 20, 26, 46, 51, 74 and mitochondrial. These early CYP genes existed side by side before the origin of cnidarians, possibly with a few additional genes interspersed. The Hox gene cluster, WNT genes, an NK gene cluster and at least one ARF gene were close neighbours to this original CYP locus. According to this evolutionary scenario, the CYP74 clan originated from animals and not from land plants nor from a common ancestor of plants and animals. The CYP7 and CYP19 families that are chordate-specific belong to CYP clans that seem to have originated in the CYP genesis locus as well, even though this requires many gene losses to explain their current distribution. The approach to uncovering the CYP genesis locus overcomes confounding effects because of gene conversion, sequence divergence, gene birth and death, and opens the way to understanding the biodiversity of CYP genes, families and subfamilies, which in animals has been obscured by more than 600 Myr of evolution.

[1]  Walter L. Miller,et al.  Human cytochromes P450 in health and disease , 2013, Philosophical Transactions of the Royal Society B: Biological Sciences.

[2]  H. Sezutsu,et al.  Origins of P450 diversity , 2013, Philosophical Transactions of the Royal Society B: Biological Sciences.

[3]  Hunter B. Fraser,et al.  Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints , 2012, Genome research.

[4]  Daniel W. A. Buchan,et al.  The tomato genome sequence provides insights into fleshy fruit evolution , 2012, Nature.

[5]  B. Lang,et al.  Rooting the eukaryotic tree with mitochondrial and bacterial proteins. , 2012, Molecular biology and evolution.

[6]  Joanna Y. Wilson,et al.  Phylogenetic and functional analyses of the cytochrome P450 family 4. , 2012, Molecular phylogenetics and evolution.

[7]  H. Sezutsu,et al.  Origins of P 450 diversity , 2012 .

[8]  P. Bajpai,et al.  Bimodal targeting of cytochrome P450s to endoplasmic reticulum and mitochondria: the concept of chimeric signals , 2011, The FEBS journal.

[9]  Alvaro J. González,et al.  The Medicago Genome Provides Insight into the Evolution of Rhizobial Symbioses , 2011, Nature.

[10]  Sean R. Eddy,et al.  Accelerated Profile HMM Searches , 2011, PLoS Comput. Biol..

[11]  A. Fujiyama,et al.  Using the Acropora digitifera genome to understand coral responses to environmental change , 2011, Nature.

[12]  J. Mullikin,et al.  Extreme mitochondrial evolution in the ctenophore Mnemiopsis leidyi: Insight from mtDNA and the nuclear genome , 2011, Mitochondrial DNA.

[13]  K. Na-Bangchang,et al.  Confutation of the existence of sequence-conserved cytochrome P450 enzymes in Plasmodium falciparum. , 2011, Acta tropica.

[14]  S. Vinogradov,et al.  What are the origins and phylogeny of plant hemoglobins? , 2011, Communicative & integrative biology.

[15]  Eun-Young Kim,et al.  Cytochrome P450 CYP2 genes in the common cormorant: Evolutionary relationships with 130 diapsid CYP2 clan sequences and chemical effects on their expression. , 2011, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[16]  Gonzalo Giribet,et al.  Higher-level metazoan relationships: recent progress and remaining questions , 2011, Organisms Diversity & Evolution.

[17]  Vincent Laudet,et al.  Origin and evolution of the ligand-binding ability of nuclear receptors , 2011, Molecular and Cellular Endocrinology.

[18]  Mary Goldman,et al.  The UCSC Genome Browser database: update 2011 , 2010, Nucleic Acids Res..

[19]  R. Feyereisen.  Arthropod CYPomes illustrate the tempo and mode in P450 evolution. , 2011, Biochimica et biophysica acta.

[20]  E. Koonin,et al.  A late origin of the extant eukaryotic diversity: divergence time estimates using rare genomic changes , 2011, Biology Direct.

[21]  D. Nelson,et al.  Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish , 2010, BMC Genomics.

[22]  J. Mullikin,et al.  The homeodomain complement of the ctenophore Mnemiopsis leidyi suggests that Ctenophora and Porifera diverged prior to the ParaHoxozoa , 2010, EvoDevo.

[23]  C. Wellman.  The invasion of the land by plants: when and where? , 2010, The New phytologist.

[24]  Sean R. Eddy,et al.  Hidden Markov model speed heuristic and iterative HMM search procedure , 2010, BMC Bioinformatics.

[25]  T. Vogt.  Phenylpropanoid biosynthesis. , 2010, Molecular plant.

[26]  M. Binder,et al.  Molecular evolution of glutamine synthetase II: Phylogenetic evidence of a non-endosymbiotic gene transfer event early in plant evolution , 2010, BMC Evolutionary Biology.

[27]  M. Martindale,et al.  Assessing the root of bilaterian animals with scalable phylogenomic methods , 2009, Proceedings of the Royal Society B: Biological Sciences.

[28]  J. Postlethwait,et al.  Automated identification of conserved synteny after whole-genome duplication. , 2009, Genome Research.

[29]  Gabriel V. Markov,et al.  Independent elaboration of steroid hormone signaling pathways in metazoans , 2009, Proceedings of the National Academy of Sciences.

[30]  Min Zhu,et al.  The oldest articulated osteichthyan reveals mosaic gnathostome characters , 2009, Nature.

[31]  Marco Fondi,et al.  A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land , 2009, Biology Direct.

[32]  N. Johnson,et al.  A synthesized pheromone induces upstream movement in female sea lamprey and summons them into traps , 2009, Proceedings of the National Academy of Sciences.

[33]  Ting Wang,et al.  The UCSC Genome Browser Database: update 2009 , 2008, Nucleic Acids Res..

[34]  Axel Meyer,et al.  Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after? , 2008, Molecular biology and evolution.

[35]  D. Nelson,et al.  The cytochrome P450 (CYP) gene superfamily in Daphnia pulex , 2009, BMC Genomics.

[36]  J. Goldstone.  Environmental sensing and response genes in cnidaria: the chemical defensome in the sea anemone Nematostella vectensis , 2008, Cell Biology and Toxicology.

[37]  Shigehiro Kuraku,et al.  Insights into Cyclostome Phylogenomics: Pre-2R or Post-2R , 2008, Zoological science.

[38]  J. Rougemont,et al.  A rapid bootstrap algorithm for the RAxML Web servers. , 2008, Systematic biology.

[39]  M. Hamberg,et al.  Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes , 2008, Nature.

[40]  Fabien Burki,et al.  Phylogenomics reveals a new ‘megagroup’ including most photosynthetic eukaryotes , 2008, Biology Letters.

[41]  Nicholas H. Putnam,et al.  The Trichoplax genome and the nature of placozoans , 2008, Nature.

[42]  Rafael D. Rosengarten,et al.  The Early ANTP Gene Repertoire: Insights from the Placozoan Genome , 2008, PloS one.

[43]  Nicholas H. Putnam,et al.  The amphioxus genome and the evolution of the chordate karyotype , 2008, Nature.

[44]  David Q. Matus,et al.  Broad phylogenomic sampling improves resolution of the animal tree of life , 2008, Nature.

[45]  Matthias Platzer,et al.  CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7 , 2008, Pharmacogenetics and genomics.

[46]  Srinivas Aluru,et al.  Large-scale maximum likelihood-based phylogenetic analysis on the IBM BlueGene/L , 2007, Proceedings of the 2007 ACM/IEEE Conference on Supercomputing (SC '07).

[47]  J. Postlethwait.  The zebrafish genome in context: ohnologs gone missing. , 2007, Journal of experimental zoology. Part B, Molecular and developmental evolution.

[48]  A. Meyer,et al.  Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications , 2007, BMC Genomics.

[49]  Takanobu Mizuta,et al.  Presence of sex steroids and cytochrome P450 genes in amphioxus. , 2007, Endocrinology.

[50]  Nicholas H. Putnam,et al.  Sea Anemone Genome Reveals Ancestral Eumetazoan Gene Repertoire and Genomic Organization , 2007, Science.

[51]  B. Degnan,et al.  The NK Homeobox Gene Cluster Predates the Origin of Hox Genes , 2007, Current Biology.

[52]  A. Knoll,et al.  Doushantuo embryos preserved inside diapause egg cysts , 2007, Nature.

[53]  James H. Thomas.  Rapid Birth–Death Evolution Specific to Xenobiotic Cytochrome P450 Genes in Vertebrates , 2007, PLoS genetics.

[54]  L. Margaretha,et al.  Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development , 2007, Development.

[55]  A. Mushegian,et al.  Intermediary metabolism in sea urchin: the first inferences from the genome sequence. , 2006, Developmental biology.

[56]  M. Scally,et al.  The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome. , 2006, Developmental biology.

[57]  R. Feyereisen,et al.  Evolution of insect P450. , 2006, Biochemical Society transactions.

[58]  Alexandros Stamatakis,et al.  RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models , 2006, Bioinform..

[59]  J. Goldstone,et al.  Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): a CYP3 line in early deuterostomes? , 2006, Molecular phylogenetics and evolution.

[60]  C. Berney,et al.  A molecular time-scale for eukaryote evolution recalibrated with the continuous microfossil record , 2006, Proceedings of the Royal Society B: Biological Sciences.

[61]  P. Holland,et al.  Breakup of a homeobox cluster after genome duplication in teleosts , 2006, Proceedings of the National Academy of Sciences.

[62]  T. Cavalier-smith,et al.  Cell evolution and Earth history: stasis and revolution , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[63]  Alexandros Stamatakis,et al.  Phylogenetic models of rate heterogeneity: a high performance computing perspective , 2006, Proceedings 20th IEEE International Parallel & Distributed Processing Symposium.

[64]  S. Munro,et al.  Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins , 2006, The Journal of cell biology.

[65]  Terrence S. Furey,et al.  The UCSC Genome Browser Database: update 2006 , 2005, Nucleic Acids Res..

[66]  J. Stegeman,et al.  A Revised Evolutionary History of the CYP1A Subfamily: Gene Duplication, Gene Conversion, and Positive Selection , 2006, Journal of Molecular Evolution.

[67]  Jordi Garcia-Fernàndez,et al.  The genesis and evolution of homeobox gene clusters , 2005, Nature Reviews Genetics.

[68]  G. Tóth,et al.  Significant microsynteny with new evolutionary highlights is detected between Arabidopsis and legume model plants despite the lack of macrosynteny , 2005, Molecular Genetics and Genomics.

[69]  R. Kahn,et al.  Arf family GTPases: roles in membrane traffic and microtubule dynamics. , 2005, Biochemical Society transactions.

[70]  John H Postlethwait,et al.  The zebrafish gene map defines ancestral vertebrate chromosomes. , 2005, Genome research.

[71]  A. Meyer,et al.  From 2R to 3R: evidence for a fish-specific genome duplication (FSGD). , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[72]  L Filipe C Castro,et al.  The genomic environment around the Aromatase gene: evolutionary insights , 2005, BMC Evolutionary Biology.

[73]  S. Munro.  The Arf-like GTPase Arl1 and its role in membrane traffic. , 2005, Biochemical Society transactions.

[74]  Paramvir S. Dehal,et al.  Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate , 2005, PLoS biology.

[75]  H. Okamoto,et al.  Retinoic acid-metabolizing enzyme Cyp26a1 is essential for determining territories of hindbrain and spinal cord in zebrafish. , 2005, Developmental biology.

[76]  M. Baker,et al.  Xenobiotics and the Evolution of Multicellular Animals: Emergence and Diversification of Ligand-Activated Transcription Factors1 , 2005, Integrative and comparative biology.

[77]  John Postlethwait,et al.  Subfunction partitioning, the teleost radiation and the annotation of the human genome. , 2004, Trends in genetics : TIG.

[78]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[79]  D. Rozman,et al.  New Aspects on Lanosterol 14α-Demethylase and Cytochrome P450 Evolution: Lanosterol/Cycloartenol Diversification and Lateral Transfer , 2004, Journal of Molecular Evolution.

[80]  D. Siveter,et al.  The Cambrian Fossils of Chengjiang, China: The Flowering of Early Animal Life , 2004 .

[81]  A. Hughes,et al.  2R or not 2R: Testing hypotheses of genome duplication in early vertebrates , 2004, Journal of Structural and Functional Genomics.

[82]  L. Maltais,et al.  Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. , 2004, Pharmacogenetics.

[83]  S Blair Hedges,et al.  BMC Evolutionary Biology BioMed Central , 2003 .

[84]  Richard J. Aldridge,et al.  The Cambrian Fossils of Chengjiang, China , 2003 .

[85]  C. Wellman,et al.  Fragments of the earliest land plants , 2003, Nature.

[86]  Douglas E. Soltis,et al.  Applying the Bootstrap in Phylogeny Reconstruction , 2003 .

[87]  Masafumi Kaneko,et al.  Cinnamate:Coenzyme A Ligase from the Filamentous Bacterium , 2002 .

[88]  A. Hughes,et al.  The temporal distribution of gene duplication events in a set of highly conserved human gene families. , 2003, Molecular biology and evolution.

[89]  D. Nelson.  Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution. , 2003, Archives of biochemistry and biophysics.

[90]  D. Siveter,et al.  New evidence on the anatomy and phylogeny of the earliest vertebrates , 2002, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[91]  J. Postlethwait,et al.  Measures of synteny conservation between species pairs. , 2002, Genetics.

[92]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[93]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[94]  T. Cavalier-smith,et al.  The neomuran origin of archaebacteria, the negibacterial root of the universal tree and bacterial megaclassification. , 2002, International journal of systematic and evolutionary microbiology.

[95]  M. Ingelman-Sundberg,et al.  Identification and Characterization of a Mitochondrial Targeting Signal in Rat Cytochrome P450 2E1 (CYP2E1)* , 2001, The Journal of Biological Chemistry.

[96]  D. Birnbaum,et al.  MetaHox gene clusters. , 2000, The Journal of experimental zoology.

[97]  O. Gotoh,et al.  Sterol 14-demethylase P450 (CYP51) provides a breakthrough for the discussion on the evolution of cytochrome P450 gene superfamily. , 2000, Biochemical and biophysical research communications.

[98]  K. Wolfe.  Robustness—it's not where you think it is , 2000, Nature Genetics.

[99]  D. Nelson,et al.  Cytochrome P450 and the individuality of species. , 1999, Archives of biochemistry and biophysics.

[100]  S. Addya,et al.  Dual Targeting Property of the N-terminal Signal Sequence of P4501A1 , 1999, The Journal of Biological Chemistry.

[101]  U. Dräger,et al.  Dorsal and ventral retinal territories defined by retinoic acid synthesis, break-down and nuclear receptor expression , 1999, Mechanisms of Development.

[102]  D. Nelson.  Metazoan cytochrome P450 evolution. , 1998, Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology.

[103]  Halverson,et al.  A neoproterozoic snowball earth , 1998, Science.

[104]  D. Kelly,et al.  Molecular diversity of sterol 14α‐demethylase substrates in plants, fungi and humans , 1998, FEBS letters.

[105]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[106]  M. Schalk,et al.  Regulation of the Cinnamate 4-Hydroxylase (CYP73A1) in Jerusalem Artichoke Tubers in Response to Wounding and Chemical Treatments , 1997, Plant physiology.

[107]  S. Scherer,et al.  Structure and mapping of the human lanosterol 14alpha-demethylase gene (CYP51) encoding the cytochrome P450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes. , 1996, Genomics.

[108]  T. Lacalli,et al.  DORSOVENTRAL AXIS INVERSION : A PHYLOGENETIC PERSPECTIVE , 1996 .

[109]  D W Nebert,et al.  P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. , 1996, Pharmacogenetics.

[110]  Moya M. Smith,et al.  Scales of thelodont and shark-like fishes from the Ordovician of Colorado , 1996, Nature.

[111]  T. Lacalli.  Dorsoventral axis inversion , 1995, Nature.

[112]  M. Cohen,et al.  A cluster of cytochrome P450 genes of the CYP6 family in the house fly. , 1995, DNA and cell biology.

[113]  S. Brenner,et al.  Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome , 1993, Nature.

[114]  U. Meyer,et al.  Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6. , 1992, Genomics.

[115]  D. Nelson,et al.  Evolution of the cytochrome P450 genes. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[116]  Dr. Susumu Ohno.  Evolution by Gene Duplication , 1970, Springer Berlin Heidelberg.