Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
BMC Evol Biol
2005 Feb 13;5:43. doi: 10.1186/1471-2148-5-43.
Show Gene links
Show Anatomy links
The genomic environment around the Aromatase gene: evolutionary insights.
Castro LF
,
Santos MM
,
Reis-Henriques MA
.
???displayArticle.abstract???
The cytochrome P450aromatase (CYP19), catalyses the aromatisation of androgens to estrogens, a key mechanism in vertebrate reproductive physiology. A current evolutionary hypothesis suggests that CYP19 gene arose at the origin of vertebrates, given that it has not been found outside this clade. The human CYP19 gene is located in one of the proposed MHC-paralogon regions (HSA15q). At present it is unclear whether this genomic location is ancestral (which would suggest an invertebrate origin for CYP19) or derived (genomic location with no evolutionary meaning). The distinction between these possibilities should help to clarify the timing of the CYP19 emergence and which taxa should be investigated. Here we determine the "genomic environment" around CYP19 in three vertebrate species Homo sapiens, Tetraodon nigroviridis and Xenopus tropicalis. Paralogy studies and phylogenetic analysis of six gene families suggests that the CYP19 gene region was structured through "en bloc" genomic duplication (as part of the MHC-paralogon formation). Four gene families have specifically duplicated in the vertebrate lineage. Moreover, the mapping location of the different paralogues is consistent with a model of "en bloc" duplication. Furthermore, we also determine that this region has retained the same gene content since the divergence of Actinopterygii and Tetrapods. A single inversion in gene order has taken place, probably in the mammalian lineage. Finally, we describe the first invertebrate CYP19 sequence, from Branchiostoma floridae. Contrary to previous suggestions, our data indicates an invertebrate origin for the aromatase gene, given the striking conservation pattern in both gene order and gene content, and the presence of aromatase in amphioxus. We propose that CYP19 duplicated in the vertebrate lineage to yield four paralogues, followed by the subsequent loss of all but one gene in vertebrate evolution. Finally, we suggest that agnathans and lophotrocozoan protostomes should be investigated for the presence of aromatase.
Figure 1. The MHC-paralogon. Two sets of paralogy regions are intact (A and B) while the remaining 2 are broken (C and D) (adapted from [20]). The map location of the MHC, CYP19 and the surrounding genes (and paralogues) is shown. In parentheses the genomic distance in megabases to the p telomere.
Figure 2. Physical maps of the genomic environment around CYP19 in Homo sapiens, Tetraodon nigroviridis and Xenopus tropicalis.
Figure 3. Neighbor-joining phylogenetic trees from alignment of the putative protein sequences of AP4E1 (A), SSC-2S (B), COL (C), DMXL (D), PPBP (E) and TMOD (F). Figures at nodes are scores from 1000 bootstrap resamplings of the data. Arrow denotes duplication timing. Ag â Anopheles gambiae; Ce â Caenorhabditis elegans; Dm â Drosophila melanogaster; Ci â Ciona intestinalis; Hs â Homo sapeins; Mm â Mus musculus; Gg â Gallus gallus; Xt â Xenopus tropicalis; Fr â Fugu rubripes; Tn â Tetraodon nigroviridis.
Figure 4. Evolutionary model for the origin of the aromatase gene family. Symbols from the two conserved DNA blocks from figure 2. Dotted line boxes denote conservation of synteny but not gene order. Black bars denote "en bloc" (or genome) duplications. Star indicates tandem duplication of TMOD2/3. Horizontal curve arrow indicates gene inversion of the DNA block containing TMOD3, TMOD2, PPBP and SCGIII.
Figure 5. Nucleotide and predicted amino acid sequence of the AmphiCYP19 (partial sequence) (A); alignment of CYP19 sequences; dashes denote insertions; black line, I-helix region; red line, Ozol's peptide region; green line, Aromatic region and blue line, Heme binding region. Bf, B. floridae, Ds, D. sabina, Am, Alligator mississippiensis, Gg, G. Gallus, Hs, H. sapiens, Mm, M. musculus, Xt, X. tropicalis, Tn, T. nigroviridis, Dr, D. rerio, Fr, Fugu rubripes (B); Neighbor-joining phylogenetic tree from the alignment of the putative protein sequences of CYP19 genes, figures at nodes are scores from 1000 bootstrap resamplings of the data ; an insertion of the TnCYP19b predicted protein sequence was kept out of the alignment (C).
Abi-Rached,
Evidence of en bloc duplication in vertebrate genomes.
2002, Pubmed
Abi-Rached,
Evidence of en bloc duplication in vertebrate genomes.
2002,
Pubmed
Almenar-Queralt,
Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle.
1999,
Pubmed
Azumi,
Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot".
2003,
Pubmed
Baker,
Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors.
2004,
Pubmed
Bertrand,
Evolutionary genomics of nuclear receptors: from twenty-five ancestral genes to derived endocrine systems.
2004,
Pubmed
Carreau,
Reproductive system: aromatase and estrogens.
2002,
Pubmed
Castro,
An antecedent of the MHC-linked genomic region in amphioxus.
2004,
Pubmed
Castro,
Fluorescent in situ hybridisation to amphioxus chromosomes.
2002,
Pubmed
Chiang,
Two Cyp19 (P450 aromatase) genes on duplicated zebrafish chromosomes are expressed in ovary or brain.
2001,
Pubmed
Coulier,
MetaHox gene clusters.
2000,
Pubmed
Danchin,
Towards the reconstruction of the bilaterian ancestral pre-MHC region.
2004,
Pubmed
Di Cosmo,
Sex steroid hormone fluctuations and morphological changes of the reproductive system of the female of Octopus vulgaris throughout the annual cycle.
2001,
Pubmed
Escriva,
Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution.
2002,
Pubmed
Furlong,
Were vertebrates octoploid?
2002,
Pubmed
Gabriel,
Alligator aromatase cDNA sequence and its expression in embryos at male and female incubation temperatures.
2001,
Pubmed
Graham-Lorence,
A three-dimensional model of aromatase cytochrome P450.
1995,
Pubmed
Hall,
Cytochromes P-450 and the regulation of steroid synthesis.
1986,
Pubmed
Hirst,
Characterization of a fourth adaptor-related protein complex.
1999,
Pubmed
Hughes,
Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history.
1999,
Pubmed
Hughes,
Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1.
1998,
Pubmed
Ijiri,
Characterization of gonadal and extra-gonadal forms of the cDNA encoding the Atlantic stingray (Dasyatis sabina) cytochrome P450 aromatase (CYP19).
2000,
Pubmed
Kasahara,
The chromosomal duplication model of the major histocompatibility complex.
1999,
Pubmed
Kortschak,
EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates.
2003,
Pubmed
Kraemer,
Mapping and structure of DMXL1, a human homologue of the DmX gene from Drosophila melanogaster coding for a WD repeat protein.
2000,
Pubmed
Kumar,
Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin- 1beta-converting enzyme-inhibitory protein.
2000,
Pubmed
Le Curieux-Belfond,
Androgen metabolism in oyster Crassostrea gigas: evidence for 17beta-HSD activities and characterization of an aromatase-like activity inhibited by pharmacological compounds and a marine pollutant.
2001,
Pubmed
Loria,
A conserved postsynaptic transmembrane protein affecting neuromuscular signaling in Caenorhabditis elegans.
2004,
Pubmed
Lundin,
Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse.
1993,
Pubmed
McPhaul,
The expression of a functional cDNA encoding the chicken cytochrome P-450arom (aromatase) that catalyzes the formation of estrogen from androgen.
1988,
Pubmed
Miyashita,
Sequence analysis and expression of the P450 aromatase and estrogen receptor genes in the Xenopus ovary.
2000,
Pubmed
,
Xenbase
Morishima,
Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens.
1995,
Pubmed
Nagano,
Rabconnectin-3, a novel protein that binds both GDP/GTP exchange protein and GTPase-activating protein for Rab3 small G protein family.
2002,
Pubmed
Neer,
The ancient regulatory-protein family of WD-repeat proteins.
1994,
Pubmed
Nelson,
Metazoan cytochrome P450 evolution.
1998,
Pubmed
Popovici,
Coparalogy: physical and functional clusterings in the human genome.
2001,
Pubmed
Popovici,
Homeobox gene clusters and the human paralogy map.
2001,
Pubmed
Santos,
Cytochrome P450 differences in normal and imposex-affected female whelk Buccinum undatum from the open North Sea.
2002,
Pubmed
Simpson,
Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage.
1997,
Pubmed
Thornton,
Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling.
2003,
Pubmed
Vienne,
Evolution of the proto-MHC ancestral region: more evidence for the plesiomorphic organisation of human chromosome 9q34 region.
2003,
Pubmed
