Theria-specific homeodomain and cis-regulatory element evolution of the Dlx3-4 bigene cluster in 12 different mammalian species.

Theria-specific homeodomain and cis-regulatory element evolution of the Dlx3-4 bigene cluster in 12 different mammalian species.
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DOI:
10.1002/jez.b.22469
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发表时间:
2012-12
影响因子:
2.2
通讯作者:
Amemiya, Chris T.
Amemiya, Chris T.
中科院分区:
生物学4区
文献类型:
--
作者:
Sumiyama, Kenta;Miyake, Tsutomu;Grimwood, Jane;Stuart, Andrew;Dickson, Mark;Schmutz, Jeremy;Ruddle, Frank H.;Myers, Richard M.;Amemiya, Chris T.

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哺乳动物Dlx3和Dlx4基因被配置为双基因簇,并且它们各自的表达模式在时间和空间上由主要位于簇的基因间区域内的顺式元件控制。先前的工作表明,小鼠和人类的 Dlx3-4 双基因簇的基因间区域存在明显保守的元件。在本文中,我们将这些分析扩展到包括 12 个额外的哺乳动物类群(包括有袋动物和单孔类动物),以便更好地定义形态上不同的哺乳动物中编码和非编码功能元件的性质和分子进化趋势。 Dlx3-4 区域对 12 个不同的感兴趣类群进行了完整测序。我们在胎盘中发挥功能的 Dlx4 基因的同源域中发现了三个兽亚特异性氨基酸替换。对基因间非编码区受限核苷酸位点的序列分析表明,许多基因间保守元件高度保守,并且在哺乳动物体内进化缓慢。相比之下,鳃弓/颅面增强子 I37-2 尽管在兽类物种中高度保守,但在单孔类和兽类共同祖先之间的分支上表现出加速进化。转基因小鼠中 I37-2 的功能分析表明,鸭嘴兽的相应区域无法驱动鳃弓的转录活性。这些观察结果与我们的分子进化数据相结合,表明 I37-2 元件中兽类特异性的间歇性变化可能有助于哺乳动物谱系基础上的颅面创新。
The mammalian Dlx3 and Dlx4 genes are configured as a bigene cluster, and their respective expression patterns are controlled temporally and spatially by cis-elements that largely reside within the intergenic region of the cluster. Previous work revealed that there are conspicuously conserved elements within the intergenic region of the Dlx3–4 bigene clusters of mouse and human. In this paper we have extended these analyses to include 12 additional mammalian taxa (including a marsupial and a monotreme) in order to better define the nature and molecular evolutionary trends of the coding and non-coding functional elements among morphologically divergent mammals. Dlx3–4 regions were fully sequenced from 12 divergent taxa of interest. We identified three theria-specific amino acid replacements in homeodomain of Dlx4 gene that functions in placenta. Sequence analyses of constrained nucleotide sites in the intergenic non-coding region showed that many of the intergenic conserved elements are highly conserved and have evolved slowly within the mammals. In contrast, a branchial arch/craniofacial enhancer I37-2 exhibited accelerated evolution at the branch between the monotreme and therian common ancestor despite being highly conserved among therian species. Functional analysis of I37-2 in transgenic mice has shown that the equivalent region of the platypus fails to drive transcriptional activity in branchial arches. These observations, taken together with our molecular evolutionary data, suggest that theria-specific episodic changes in the I37-2 element may have contributed to craniofacial innovation at the base of the mammalian lineage.
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