Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.
Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.
复制标题
DOI：
10.1186/s12915-015-0165-x
复制
发表时间：
2015-08-01
期刊：
影响因子：
5.4
通讯作者：
Holland PW
中科院分区：
文献类型：
--
作者：
Marlétaz F;Maeso I;Faas L;Isaacs HV;Holland PW
全基因组复制在脊椎动物进化中的功能后果尚不完全清楚。例如，目前尚不清楚为什么在一些基因家族中保留了旁系，而在另一些基因家族中却大量丢失。Cdx同源盒基因编码保守的转录因子，控制不同两侧动物的后侧发育。这些基因是副甲氧杆菌基因簇的一部分。多个Cdx拷贝在基因组复制后被保留，这就提出了关于功能分化、重叠和冗余分别如何影响它们的保留和进化命运的问题。我们利用热带非洲爪蟾单次和三次morpholino敲除和RNA-seq检测了三个脊椎动物Cdx基因之间的调节和功能重叠程度。我们发现Cdx4对基因表达的影响比其他的要大得多，包括对FGF和Wnt基因的强烈调节作用。功能注释揭示了每个基因的不同和重叠的作用和微妙的不同的作用时间窗口。这些数据还揭示了Cdx基因对Hox基因的共线性作用，Hox的1和2组被抑制，而Hox的5到11组的激活增加。我们还强调了复制基因调节不同的同源靶点的情况，揭示了全基因组复制后通路的细化。尽管有共同的核心途径，Cdx同源物在发育过程中获得了不同的调节作用。这意味着旁系基因之间的功能重叠程度相对较低，在研究重复基因的功能进化时，单独使用基因表达模式应该谨慎。因此，我们认为，在脊椎动物的早期进化中，全基因组复制后，发育程序被广泛地重新连接。本文的在线版本（doi:10.1186/s12915-015-0165-x）包含补充材料，可供授权用户使用。
The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates. The online version of this article (doi:10.1186/s12915-015-0165-x) contains supplementary material, which is available to authorized users.