Castro L Filipe C, Santos Miguel M, Reis-Henriques Maria A
CIIMAR - Centre of Marine and Environmental Research, Rua dos Bragas 289, 4050-123, Oporto, Portugal.
BMC Evol Biol. 2005 Aug 12;5:43. doi: 10.1186/1471-2148-5-43.
The cytochrome P450 aromatase (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.
细胞色素P450芳香化酶（CYP19）催化雄激素向雌激素的芳香化反应，这是脊椎动物生殖生理学中的关键机制。当前的一种进化假说认为，CYP19基因起源于脊椎动物出现之时，因为在该进化枝之外尚未发现该基因。人类CYP19基因位于一个推测的主要组织相容性复合体旁系同源区域（人染色体15q）。目前尚不清楚这种基因组定位是祖传的（这意味着CYP19起源于无脊椎动物）还是衍生的（基因组定位无进化意义）。区分这两种可能性将有助于阐明CYP19出现的时间以及应该研究哪些分类群。
在此，我们确定了三种脊椎动物——智人、黑青斑河豚和热带爪蟾——中CYP19周围的“基因组环境”。对六个基因家族的旁系同源性研究和系统发育分析表明，CYP19基因区域是通过“整体”基因组重复构建的（作为主要组织相容性复合体旁系同源区域形成的一部分）。四个基因家族在脊椎动物谱系中发生了特异性重复。此外，不同旁系同源物的定位与“整体”重复模型一致。此外，我们还确定，自辐鳍鱼纲和四足动物分化以来，该区域保留了相同的基因组成。基因顺序发生了一次单一倒位，可能发生在哺乳动物谱系中。最后，我们描述了佛罗里达文昌鱼的首个无脊椎动物CYP19序列。
与之前的观点相反，我们的数据表明芳香化酶基因起源于无脊椎动物，这是鉴于基因顺序和基因组成中显著的保守模式以及文昌鱼中存在芳香化酶。我们提出，CYP19在脊椎动物谱系中发生重复产生了四个旁系同源物，随后在脊椎动物进化过程中除一个基因外的所有基因都丢失了。最后，我们建议研究无颌类动物和触手冠动物原口动物中是否存在芳香化酶。
