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Conservation and Divergence of Regulatory Strategies at Hox Loci and the Origin of Tetrapod Digits

机译:Hox基因座和四足动物数字起源的监管策略的保存和分歧

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The evolution of tetrapod limbs from fish fins enabled the conquest of land by vertebrates and thus represents a key step in evolution. Despite the use of comparative gene expression analyses, critical aspects of this transformation remain controversial, in particular the origin of digits. Hoxa and Hoxd genes are essential for the specification of the different limb segments and their functional abrogation leads to large truncations of the appendages. Here we show that the selective transcription of mouse Hoxa genes in proximal and distal limbs is related to a bimodal higher order chromatin structure, similar to that reported for Hoxd genes, thus revealing a generic regulatory strategy implemented by both gene clusters during limb development. We found the same bimodal chromatin architecture in fish embryos, indicating that the regulatory mechanism used to pattern tetrapod limbs may predate the divergence between fish and tetrapods. However, when assessed in mice, both fish regulatory landscapes triggered transcription in proximal rather than distal limb territories, supporting an evolutionary scenario whereby digits arose as tetrapod novelties through genetic retrofitting of preexisting regulatory landscapes. We discuss the possibility to consider regulatory circuitries, rather than expression patterns, as essential parameters to define evolutionary synapomorphies.
机译:从鱼鳍进化出四足动物肢体使脊椎动物能够征服土地,因此代表了进化的关键一步。尽管使用了比较基因表达分析,但这种转化的关键方面仍存在争议,尤其是数字的起源。 Hoxa和Hoxd基因对于指定不同的肢体节段必不可少,其功能废除会导致附件的大截断。在这里,我们显示小鼠Hoxa基因在近端和远端肢体中的选择性转录与双峰高阶染色质结构有关,与报道的Hoxd基因相似,从而揭示了在肢体发育过程中两个基因簇均实现的通用调控策略。我们在鱼胚胎中发现了相同的双峰染色质结构,这表明用于模式四足动物肢体的调控机制可能早于鱼与四足动物之间的差异。然而,当在小鼠中进行评估时,两条鱼的调控景观都触发了近端而非远端肢体区域的转录,从而支持了进化场景,即通过对已有调控景观进行基因改造,使数字成为四足动物新奇事物。我们讨论了将调节电路而不是表达模式作为定义进化突触的基本参数的可能性。

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