Additional hox clusters in the zebrafish:: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes
Additional hox clusters in the zebrafish:: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes
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DOI：
10.1046/j.1525-142x.2001.003003127.x
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发表时间：
2001-05-01
影响因子：
2.9
通讯作者：
Ho, RK
中科院分区：
文献类型：
--
作者：
Bruce, AEE;Oates, AC;Ho, RK
后生动物身体计划的进化涉及HOX基因的变化，HOX基因参与了体轴的图案化，并在结构和表达方面表现出显著的进化保守性。无脊椎动物只有一个HOX簇，而四足动物有四个簇。斑马鱼有七个互不相连的Hox簇，这一发现很难与由Hox簇数反映的基因组复杂性和形态复杂性是因果联系的概念相一致，因为斑马鱼的身体平面并不明显比老鼠或人类的复杂。为什么斑马鱼中额外的HOX基因是保守的？为了解决这些额外的斑马鱼HOX基因的作用，我们研究了重复的HOXB5基因，hoxB5a和hoxB5b。当一个基因获得新的功能时(新功能化)，或者当祖先的功能在两个重复的基因之间分配时(亚功能化)，就可能发生基因复制的保守。HoxB5a和hoxB5b在不同的结构域中表达，它们的组合表达结构域与其他物种中单个HOXB5基因的表达结构域惊人地相似。结果表明，hoxB5a和hoxB5b在早期发育过程中具有相同的生化特性。从这些研究中，我们得出结论，hoxB5a和hoxB5b的保守很可能是祖先的HOXB5功能在这两个基因之间分裂的结果，而没有明显的生化活性变化。这些结果暗示了斑马鱼中额外的HOX基因和簇的难题的解决方案，因为如果斑马鱼中的任何额外的HOX基因类似地被亚功能化，它们不太可能提供新的遗传功能。因此，大多数额外的斑马鱼Hox簇可能带来的形态复杂性可能不会显著大于四个四足动物簇带来的形态复杂性。
The evolution of metazoan body plans has involved changes to the Hox genes, which are involved in patterning the body axis and display striking evolutionary conservation of structure and expression. Invertebrates contain a single Hox cluster whereas tetrapods possess four clusters. The zebrafish has seven unlinked hox clusters, a finding that is difficult to reconcile with the notion that genomic complexity, reflected by Hox cluster number, and morphological complexity are causally linked, as the body plan of the zebrafish is not obviously more complex than that of the mouse or human. Why have the additional hox genes in zebrafish been conserved?To address the role of these additional zebrafish hox genes, we have examined the duplicate hoxB5 genes, hoxB5a, and hoxB5b. Conservation of gene duplicates can occur when one gene acquires a new function (neofunctionalization), or when the ancestral function is divided between the two duplicates (subfunctionalization). hoxB5a and hoxB5b are expressed in distinct domains, and their combined expression domain is strikingly similar to that of single Hoxb5 genes in other species. The biochemical functions encoded by the two genes were studied by overexpression, which resulted in identical developmental defects in the anterior hindbrain and cranial neural crest, suggesting strongly that hoxB5a and hoxB5b have equivalent biochemical properties with respect to early development. From these studies, we conclude that conservation of hoxB5a and hoxB5b is likely the result of division of the ancestral Hoxb5 function between the two genes, without significant changes in biochemical activity. These results suggest a resolution to the conundrum of the extra hox genes and clusters in the zebrafish, since if any of the additional hox genes in the zebrafish are similarly subfunctionalized, they are unlikely to supply novel genetic functions. Thus, the morphological complexity potentially conferred by the majority of additional zebrafish hox clusters may not be substantially greater than that conferred by the four tetrapod clusters.