Phylogenetic Studies of the Homeodomain Protein Family

该研究计划的重点是蛋白质同源结构域组的计算分析，这些蛋白质在后生动物发育过程中的身体计划，模式形成和细胞命运决定的规范中发挥着重要作用。各种生物信息学方法用于了解这些蛋白质的进化和功能及其在人类疾病中的作用。 同源异型框（或Hox）基因在一系列系统发育分类群中以保守的基因组簇形式组织，并被认为部分负责形成初级体轴。在进化过程中，这些Hox基因的功能多样化有助于动物身体计划的多样化。为了研究Hox基因的起源和早期进化以及“Hox密码”，我们将重点放在海葵Nematostella上。刺胞动物，包括珊瑚，海葵和水母，构成了一个外群bilaterians动物具有双边对称性，并有可能提供独特的见解早期Hox进化。我们已经发现系统发育的证据表明，一个基本的Hox代码在刺胞动物bilaterian祖先中发挥了作用，在图案的动物的主要（可能是次要的）身体轴。此外，由于这种Hox代码的强大稳定选择，尽管在一系列令人眼花缭乱的动物形式中存在了超过5亿年，但某些核心特征仍然得到了保持。此外，我们已经研究了Wnt基因在祖先后生动物轴向模式中的可能作用，基因功能被认为早于Hox系统。强有力的证据表明，Hox基因被“增选”到这条途径之间的某个时候，他们的起源和最后的共同祖先刺胞动物和bilaterians。目前的工作重点是使用下一代测序技术，以进一步了解一些对发展至关重要的蛋白质家族的进化。 作为我们对蛋白质同源结构域类研究的产物，我们已经开发并继续维护同源结构域资源。同源结构域资源是同源结构域家族的序列，结构，相互作用，基因组和功能信息的精选集合。目前的版本建立在以前的版本，通过添加新的，完整的套同源结构域序列从完全测序的基因组，现有的策划同源结构域信息的扩展和改善数据的可访问性，通过更好的搜索工具和更完整的数据集成。该版本包含1534个全长含同源结构域序列，93个实验衍生的同源结构域结构，101个同源结构域蛋白质相互作用，107个同源结构域DNA结合位点和206个与人类遗传疾病有关的同源结构域蛋白质。Homeodomain资源可在http：/research.nhgri.nih.gov/homeodomain/上免费获得。

This research program focuses on the computational analysis of the homeodomain group of proteins, which play a fundamental role in the specification of body plan, pattern formation, and cell fate determination during metazoan development. A variety of bioinformatic approaches are used to understand the evolution and function of these proteins and their role in human disease. Homeobox (or Hox) genes are organized in conserved genomic clusters across a range of phylogenetic taxa and are considered partially responsible for patterning the primary body axis. Over evolutionary time, the functional diversification of these Hox genes has contributed to the diversification of animal body plans. To investigate the origin and early evolution of Hox genes and the "Hox code," we have focused on the sea anemone Nematostella. Cnidarians, including corals, sea anemones, and jellyfish, constitute an outgroup to bilaterians animals having bilateral symmetry and have the potential to provide unique insights into early Hox evolution. We have found phylogenetic evidence suggesting that a rudimentary Hox code in the cnidarian-bilaterian ancestor played a role in patterning the animal's primary (and possibly secondary) body axis. Moreover, thanks to strong stabilizing selection on this Hox code, certain core characteristics have been maintained despite being deployed in a bewildering array of animal forms for over a half billion years. In addition, we have examined the possible role of Wnt genes in ancestral metazoan axial patterning, gene functions thought to pre-date the Hox system. Strong evidence suggests that Hox genes were "co-opted" into this pathway sometime between their origin and the last common ancestor of cnidarians and bilaterians. Current work is focused on using next-generation sequencing technologies to further understand the evolution of a number of protein families that are important to development. As an outgrowth of our studies on the homeodomain class of proteins, we have developed and continue to maintain the Homeodomain Resource. The Homeodomain Resource is a curated collection of sequence, structure, interaction, genomic and functional information on the homeodomain family. The current version builds upon previous versions by the addition of new, complete sets of homeodomain sequences from fully sequenced genomes, the expansion of existing curated homeodomain information and the improvement of data accessibility through better search tools and more complete data integration. This release contains 1534 full-length homeodomain-containing sequences, 93 experimentally derived homeodomain structures, 101 homeodomain proteinprotein interactions, 107 homeodomain DNA-binding sites and 206 homeodomain proteins implicated in human genetic disorders. The Homeodomain Resource is freely available at http:/research.nhgri.nih.gov/homeodomain/.