Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function
Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function
复制标题
DOI：
10.1073/pnas.1005129107
复制
发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Manley, Nancy R.
中科院分区：
文献类型：
--
作者：
Chen, Lizhen;Zhao, Peng;Manley, Nancy R.
Hox基因在胚胎发生过程中起着进化保守的作用，在指定轴的位置。一个流行的范例是，Hox基因表达的变化驱动后生动物身体计划的进化。跨物种的Hox功能的保护，并在一个物种内的旁系同源Hox基因，支持功能等价的模型。在这份报告中，我们表明，斑马鱼hoxa 3a（zfhoxa 3a）从小鼠Hoxa 3基因座表达可以取代小鼠Hoxa 3在某些组织中，但在其他人有不同的或无效的表型。我们进一步表明，通过使用编码嵌合蛋白的等位基因，这种差异主要映射到zfhoxa 3a的C-末端结构域。我们的数据意味着，小鼠和斑马鱼的蛋白质有很大的分歧，因为他们最后的共同祖先，它们之间的主要区别在于C-末端结构域。我们的数据进一步表明，Hox蛋白的功能可以在不同的细胞类型中独立进化，或用于特定的功能。zfhoxa 3a不能执行小鼠Hoxa 3的所有正常作用，说明Hox直系同源物并不总是功能上可互换的。
Hox genes play evolutionarily conserved roles in specifying axial position during embryogenesis. A prevailing paradigm is that changes in Hox gene expression drive evolution of metazoan body plans. Conservation of Hox function across species, and among paralogous Hox genes within a species, supports a model of functional equivalence. In this report, we demonstrate that zebrafish hoxa3a (zfhoxa3a) expressed from the mouse Hoxa3 locus can substitute for mouse Hoxa3 in some tissues, but has distinct or null phenotypes in others. We further show, by using an allele encoding a chimeric protein, that this difference maps primarily to the zfhoxa3a C-terminal domain. Our data imply that the mouse and zebrafish proteins have diverged considerably since their last common ancestor, and that the major difference between them resides in the C-terminal domain. Our data further show that Hox protein function can evolve independently in different cell types or for specific functions. The inability of zfhoxa3a to perform all of the normal roles of mouse Hoxa3 illustrates that Hox orthologues are not always functionally interchangeable.