Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals
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DOI：
10.1073/pnas.0802355105
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发表时间：
2008-09-30
影响因子：
11.1
通讯作者：
Wagner, Gunter P.
中科院分区：
文献类型：
--
作者：
Lynch, Vincent J.;Tanzer, Andrea;Wagner, Gunter P.
基因调控的进化变化可能是由顺式调控元件的变化引起的，导致基因的时间和空间表达的差异，或导致新功能的转录因子编码区的差异，或两者兼而有之。尽管越来越多的证据支持顺式调控进化的重要性，但蛋白质介导的新发育途径进化的例子尚未得到证实。在这里，我们研究了子宫内膜细胞中催乳素（PRL）表达的进化，这对于真兽类哺乳动物的胎盘/妊娠至关重要，并且是转录因子 HoxA-11 的直接调节靶标。在这里，我们表明（i）子宫内膜PRL表达是胎盘哺乳动物的衍生特征，（ii）PRL调节基因HoxA-11在真兽类哺乳动物的干谱系中经历了一段强正选择时期，以及（iii）只有来自胎盘哺乳动物的HoxA-11蛋白，包括重建的祖先真兽基因，能够通过子宫内膜细胞中使用的启动子上调PRL。相比之下，来自重建的兽类祖先、负鼠、鸭嘴兽和鸡的 HoxA-11 无法上调 PRL 表达。这些结果表明，新基因表达结构域的进化不仅由顺式调控元件的进化介导，而且还可能需要转录因子蛋白本身的进化变化。
Evolutionary change in gene regulation can result from changes in cis-regulatory elements, leading to differences in the temporal and spatial expression of genes or in the coding region of transcription factors leading to novel functions or both. Although there is a growing body of evidence supporting the importance of cis-regulatory evolution, examples of protein-mediated evolution of novel developmental pathways have not been demonstrated. Here, we investigate the evolution of prolactin (PRL) expression in endometrial cells, which is essential for placentation/pregnancy in eutherian mammals and is a direct regulatory target of the transcription factor HoxA-11. Here, we show that (i) endometrial PRL expression is a derived feature of placental mammals, (ii) the PRL regulatory gene HoxA-11 experienced a period of strong positive selection in the stem-lineage of eutherian mammals, and (iii) only HoxA-11 proteins from placental mammals, including the reconstructed ancestral eutherian gene, are able to up-regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11 from the reconstructed therian ancestor, opossum, platypus, and chicken are unable to up-regulate PRL expression. These results demonstrate that the evolution of novel gene expression domains is not only mediated by the evolution of cis-regulatory elements but can also require evolutionary changes of transcription factor proteins themselves.