Evolutionary divergence of a Hoxa2b hindbrain enhancer in syngnathids mimics results of functional assays
Evolutionary divergence of a Hoxa2b hindbrain enhancer in syngnathids mimics results of functional assays
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DOI：
10.1007/s00427-021-00676-x
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发表时间：
2021-05
影响因子：
2.4
通讯作者：
A. Fuiten;W. Cresko
中科院分区：
文献类型：
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作者：
A. Fuiten;W. Cresko
Hoxa2基因在发育过程中提供关键的模式信号，其调控和功能已被广泛研究。我们报告了Syngnathidae家族(海豚、海马、笛马、海豚)中一个高度保守的后脑hoxa2benhancer元件的显著序列差异。我们比较了海湾海豚和两种海马鱼与其他八种鱼以及人和老鼠的HOX顺式调节元件的变异。我们注释了三种海马、四种海豚和一种幽灵海豚的hoxa2苯环元件结合位点。最后，我们对Hoxa2b在海湾海豚胚胎中的表达进行了原位杂交分析。我们发现，所有被研究的合体鱼类都有一个修改的菱形4hoxa2 bbenhancer元件，尽管这个元件在之前研究的所有脊椎动物中都被发现高度保守。在几种海豚和海马中，hoxa2结合元件的结合元件序列基序和结合元件之间的间距已经被修改，并且在幽灵海豚从合并体的其余分支分裂后，Prep/Meis结合位点的丢失和进一步的空间缩短发生了。我们发现，在海湾海豚胚胎发育中，该基因在菱形核4中的表达低于周围的菱形核，这反映了之前发表的对该增强子的功能测试。我们的发现突出了研究高度派生的、多样化的分类群对于理解基因调控进化的好处，并支持这样的假设，即自然突变可以以与表型多样性潜在相关的方式发生在高度保守的途径中。
Hoxa2genes provide critical patterning signals during development, and their regulation and function have been extensively studied. We report a previously uncharacterized significant sequence divergence of a highly conserved hindbrainhoxa2benhancer element in the family syngnathidae (pipefishes, seahorses, pipehorses, seadragons). We compared thehox cis-regulatory element variation in the Gulf pipefish and two species of seahorse against eight other species of fish, as well as human and mouse. We annotated thehoxa2benhancer element binding sites across three species of seahorse, four species of pipefish, and one species of ghost pipefish. Finally, we performed in situ hybridization analysis ofhoxa2bexpression in Gulf pipefish embryos. We found that all syngnathid fish examined share a modified rhombomere 4hoxa2benhancer element, despite the fact that this element has been found to be highly conserved across all vertebrates examined previously. Binding element sequence motifs and spacing between binding elements have been modified for thehoxa2benhancer in several species of pipefish and seahorse, and that the loss of the Prep/Meis binding site and further space shortening happened after ghost pipefish split from the rest of the syngnathid clade. We showed that expression of this gene in rhombomere 4 is lower relative to the surrounding rhombomeres in developing Gulf pipefish embryos, reflecting previously published functional tests for this enhancer. Our findings highlight the benefits of studying highly derived, diverse taxa for understanding of gene regulatory evolution and support the hypothesis that natural mutations can occur in deeply conserved pathways in ways potentially related to phenotypic diversity.