Bioinformatics & Medical Informatics Team, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Biol Direct. 2010 Aug 4;5:49. doi: 10.1186/1745-6150-5-49.
Wnt5 genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that Wnt5 gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two Wnt5 paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics.
In this study, the phylogeny of Wnt5 genes was investigated in species belonging to protostomia and deuterostomia. Furthermore, an in silico regulatory region analysis of Wnt5 paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the Wnt5 gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind.
Results and observations presented in this study, allow us to conclude that during evolution, the Wnt5 gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the Wnt5 orthologs do not share the same function during pancreas development. As a final remark, we suggest that an in silico comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs.
Wnt5 基因属于大型 Wnt 家族，其编码的蛋白质参与了几种肿瘤发生和发育过程。系统发育分析表明，Wnt5 基因在有颌类与无颌类分化时发生了复制。有趣的是，一些物种的实验数据表明，两个 Wnt5 旁系同源物中只有一个参与了内分泌胰腺的发育。本文旨在通过比较基因组学重新检验 Wnt5 发育调节剂的系统发育历史，并研究旁系同源物之间的功能转变。
本研究在原口动物和后口动物的物种中研究了 Wnt5 基因的系统发育。此外，我们还对 Wnt5 旁系同源物的调控区进行了计算机分析，仅限于那些具有胰岛素分泌细胞和胰腺的物种，涵盖了从无颌类到有颌类的进化距离。我们的结果证实了 Wnt5 基因的复制，并且还表明该复制事件还包括上游区域。此外，在这个后者区域内，检测到一个保守模块，已知该模块与参与胚胎胰腺形成的转录因子复合物结合。
本研究的结果和观察结果表明，在进化过程中，Wnt5 基因在早期脊椎动物中发生了复制，并且一些旁系同源物在其调控区域内保守了一个模块，该模块与胰腺的胚胎发育功能相关。有趣的是，我们的结果为为什么 Wnt5 直系同源物在胰腺发育过程中不具有相同的功能提供了一个可能的解释。最后，我们建议，特别是当与已发表的实验数据结合使用时，对调控区域进行计算机比较分析是解释旁系同源物之间功能转变的一种有效方法。
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