Evo-devo: Relaxed constraints on Hox gene clustering during evolution
Evo-devo: Relaxed constraints on Hox gene clustering during evolution
复制标题
Evo-devo：放宽了进化过程中Hox基因聚类的限制
DOI：
10.1038/sj.hdy.6800624
复制
发表时间：
2005
期刊：
影响因子：
3.8
通讯作者：
B. Galliot
中科院分区：
文献类型：
--
作者：
B. Galliot
对 Oikopleura 中 Hox 基因的一项新研究表明，这些发育基因分散在整个基因组中，而不是像大多数动物那样聚集在一起。 Hox 基因最初在果蝇中被鉴定为分组调节基因，称为同源异型基因。它们在发育过程中遵循共线性规则对位置信息进行编码，也就是说，它们在簇中的物理位置与它们沿着发育胚胎的前后（AP）轴表达的物理顺序平行（Lewis，1978）。几年后，它们在果蝇和脊椎动物中的分子特征证明，它们编码的蛋白质通过同源结构域结合 DNA，同源结构域是一个由 60 个高度进化保守的氨基酸组成的结构域。此外，哺乳动物具有相同的染色体簇结构，其中发现了四个与果蝇同源的 Hox 簇拷贝。随后对切片和整体胚胎进行的转录分析证明了共线性规则的保守性（McGinnis 和 Krumlauf，1992）。因此，Hox 基因似乎可以在所有动物发育的早期阶段提供身体结构的共同分子表征。这被称为系统发育阶段，在此期间来自不同物种的胚胎往往彼此相似（Slack 等，1993）。因此，预计即使在所有两侧对称动物的共同祖先中，Hox 基因簇也可能具有这种至关重要的发育作用。然而，在脊椎动物中，空间共线性规则只是故事的一部分。在哺乳动物中，研究表明，Hox 基因在发育过程中激活的时间顺序也对应于这些基因在基因组簇中排列的顺序（Kmita 和 Duboule，2003）。在果蝇胚胎中没有观察到这种时间调节，其中 Hox 基因分裂成两个半簇并同时激活。对小鼠的基因操作表明，Hox 基因的聚集组织是实现如此严格的时间控制所必需的。相比之下，在其他许多情况下，Hox 聚类并不是实现正确空间表达所必需的（参见 Kmita 和 Duboule，2003 年）。那么哪些因素决定Hox基因是否需要聚类呢？只有对不同门类（例如线虫秀丽隐杆线虫）中Hox基因的组织、功能和调控进行详细分析，才有可能明确回答这个问题。就秀丽隐杆线虫而言，几个 Hox 基因已经丢失，同源域序列也显着分化（Aboobaker 和 Blaxter，2003）。这些破坏与秀丽隐杆线虫中的 Hox 基因不再传递沿 AP 轴的位置信息这一事实相关。在最近的一篇论文中，Seo 和同事 (Seo et al, 2004) 描述了被囊动物 Oikopleura dioica 中 Hox 复合体的类似分解，其中九个 Hox 基因实际上并不代表完整的 Hox 簇。两个属于最前面的两个组（唇/ PG-1、pb/PG-2），一个可能与指定躯干的 Hox 基因（Dfd/PG-4 到 PG-7）不同，六个与最靠后的组（PG-11 到 PG-13）相关。另一种被囊类动物海鞘也丢失了中央Hox基因，这表明这一进化事件可能发生在一个共同的被囊类祖先中，该群体与导致脊椎动物的谱系分歧。相比之下，Oikopleura 中后部 Hox 基因的扩增可能与尾部（脊索动物特有的特征）的进化相关。因此，这种情况类似于蠕虫中所见的情况，但发生在不同的脊索动物门中，但与脊椎动物相距不远。令人惊讶的是，即使没有 Hox 基因的基因组聚类，作者也报告了明显的空间共线性，尽管尚未观察到时间共线性。然而，由于这些Hox基因的表达仅限于尾部区域，其中一些基因表现出严格的组织和细胞特异性，因此Oikopleura Hox基因在沿AP轴传递位置信息方面的明确功能尚未得到证实。换句话说，这些基因在这种衍生动物中可能发挥着相当不同的作用。无论如何，这些结果支持 Hox 基因聚类和时间共线性之间的联系。进化过程中空间和时间共线性出现的时间仍然是一个悬而未决的问题。一方面，Hox 基因对于胚胎发育可能是可有可无的，但对于成体身体计划的形成却不是必需的，正如在经历间接发育的物种中所证明的那样，其中成体身体计划源自幼虫的有限部分（Peterson 等人，2000）。在这种情况下，Hox 基因的表达不是在幼虫形成过程中检测到的，而是在随后形成成虫身体计划的幼虫组织中检测到的。但同样，规则似乎根据环境而变化：在多毛类环节动物 Chaetopterus variopedatus 幼虫中，Hox 基因似乎遵循空间和时间共线性规则，而在海胆 Strongylocentrous purpuratus 幼虫中，共线性仅限于中胚层衍生物（Arenas-Mena 等，2000）。另一方面，Hox 以及非 Hox 同源盒基因的聚类可能对应于一个非常古老的事件（Holland，2001）。这种祖先聚类是否依赖于转录控制仍有待检验。在早于两侧对称动物门的刺胞动物中，Hox相关基因被表达为发育基因（Finnerty等，2004），因此对该门中它们的染色体组织、功能和调节进行系统和比较分析可以帮助识别众多两侧对称动物变异中共同的原始主题。 B Galliot 就职于日内瓦大学动物学和动物生物学系，地址：30, quai Ernest-Ansermet,Geneva 4,Switzerland。
A new study of Hox genes in Oikopleura reveals these developmental genes to be scattered across the genome, rather than clustered, as found in most animals. Hox genes were initially identified in Drosophila as grouped regulatory genes, known as homeotic genes. They encode positional information during development following the colinearity rule, that is, their physical location in the cluster parallels the physical order of their expression along the anterior to posterior (AP) axis of the developing embryo (Lewis, 1978). Some years later, their molecular characterisation in both Drosophila and vertebrates proved that they code for proteins that bind DNA through the homeodomain, a domain of 60 highly evolutionarily conserved amino acids. Furthermore, mammals have the same clustered chromosomal organisation, where four copies of the Hox cluster, homologous to that of Drosophila, were found. Transcriptional analyses performed on sectioned and whole-mount embryos subsequently demonstrated the conservation of the colinearity rule (McGinnis and Krumlauf, 1992). So it seemed that Hox genes might provide a common molecular representation of the body plan at an early stage of the development of all animals. This is referred to as the phylotypic stage, during which embryos from distinct species tend to resemble to each other (Slack et al, 1993). Consequently, it was expected that the Hox gene cluster might have had this crucial developmental role even in the common ancestor of all bilaterally symmetrical animals. However, in vertebrates, the spatial colinearity rule turned out to be only part of the story. In mammals, it was shown that the temporal order of activation of the Hox genes during development also corresponds to the order that these genes are arrayed in the genomic cluster (Kmita and Duboule, 2003). This temporal regulation is not observed in Drosophila embryos, where Hox genes are split into two halfclusters and are activated simultaneously. Genetic manipulations in mice show that the clustered organisation of Hox genes is required to implement such a tight temporal control. In contrast, Hox clustering is not necessary to achieve a proper spatial expression in other numerous cases (see in Kmita and Duboule, 2003). So what factors determine whether Hox genes need to be clustered or not? Only a detailed analysis of the organisation, function and regulation of Hox genes in diverse phyla where the clustered organisation of Hox genes has obviously been disrupted, such as in the nematode Caenorhabditis elegans, is likely to definitively answer this question. In the case of C. elegans, several Hox genes have been lost and homeodomain sequences have significantly diverged (Aboobaker and Blaxter, 2003). These disruptions correlate with the fact that Hox genes in C. elegans no longer deliver positional information along the AP axis. In a recent paper, Seo and co-workers (Seo et al, 2004) describe a similar disintegration of the Hox complex in the tunicate Oikopleura dioica, where the nine Hox genes actually do not represent a complete Hox cluster. Two belong to the two most anterior groups (labial/ PG-1, pb/PG-2), one might have diverged from the Hox genes that specify the trunk (Dfd/PG-4 to PG-7) and six are related to the most posterior groups (PG-11 to PG-13). Ciona, another tunicate species, has also lost the central Hox genes, which indicates that this evolutionary event might have occurred in a common tunicate ancestor, this group diverged from the lineage that led to vertebrates. In contrast, amplification of the posterior Hox genes in Oikopleura might correlate with the evolution of the tail, a chordate-specific feature. This situation is thus similar to that seen in worms, but occurs in a chordate phylum distinct, yet not far away from vertebrates. Surprisingly, even without genomic clustering of Hox genes, the authors report an apparent spatial colinearity, although temporal colinearity is nevertheless not observed. However, as expression of these Hox genes is restricted to the tail region, with some of them exhibiting a strict tissue and cell specificity, a clear function of Oikopleura Hox genes in delivering positional information along the AP axis is as yet to be proven. In other words, these genes may serve a rather different task in such a derived animal. In any case, these results support the link between clustering of Hox genes and temporal colinearity. The time at which spatial and temporal colinearities emerged during evolution remains an open question. On the one hand, Hox genes might be dispensable for embryonic development but not for adult body plan formation, as demonstrated in species undergoing an indirect development, where the adult body plan derives from a limited portion of the larva (Peterson et al, 2000). In such cases, expression of Hox genes was detected not during larva formation but subsequently in larval tissues that go on to form the adult body plan. But there again, rules seem to vary according to the context: in the polychaete annelid Chaetopterus variopedatus larva, Hox genes seem to follow both the spatial and temporal colinearity rules, while in the sea urchin Strongylocentrous purpuratus larva, colinearity is restricted to mesodermal derivatives (Arenas-Mena et al, 2000). On the other hand, clustering of Hox as well as non-Hox homeobox genes likely corresponds to a very ancestral event (Holland, 2001). Whether or not this ancestral clustering was dependent on transcriptional control remains to be examined. In cnidarians, a phylum that predated bilaterians, Hox-related genes are expressed as developmental genes (Finnerty et al, 2004), hence a systematic and comparative analysis of their chromosomal organisation, function and regulation in this phylum could help identifying the common original theme among the numerous bilaterian variations. B Galliot is at the Department of Zoology and Animal Biology, University of Geneva, 30, quai Ernest-Ansermet, Geneva 4, Switzerland.