Laboratoire Evolution, Génomes et Spéciation, UPR 9034 Centre National de la Recherche Scientifique and Université Paris Diderot-Paris 7, 91198 Gif sur Yvette, France.
Mol Biol Evol. 2010 Dec;27(12):2829-38. doi: 10.1093/molbev/msq172. Epub 2010 Jul 8.
It is now well established that there were four Hox gene clusters in the genome of the last common ancestor of extant gnathostomes. To better understand the evolution of the organization and expression of these genomic regions, we have studied the Hox gene clusters of a shark (Scyliorhinus canicula). We sequenced 225,580 expressed sequence tags from several embryonic cDNA libraries. Blast searches identified corresponding transcripts to almost all the HoxA, HoxB, and HoxD cluster genes. No HoxC transcript was identified, suggesting that this cluster is absent or highly degenerate. Using Hox gene sequences as probes, we selected and sequenced seven clones from a bacterial artificial chromosome library covering the complete region of the three gene clusters. Mapping of cDNAs to these genomic sequences showed extensive alternative splicing and untranslated exon sharing between neighboring Hox genes. Homologous noncoding exons could not be identified in transcripts from other species using sequence similarity. However, by comparing conserved noncoding sequences upstream of these exons in different species, we were able to identify homology between some exons. Some alternative splicing variants are probably very ancient and were already coded for by the ancestral Hox gene cluster. We also identified several transcripts that do not code for Hox proteins, are probably not translated, and all but one are in the reverse orientation to the Hox genes. This survey of the transcriptome of the Hox gene clusters of a shark shows that the high complexity observed in mammals is a gnathostome ancestral feature.
现在已经确定，现存有颌类动物的最后共同祖先的基因组中有四个 Hox 基因簇。为了更好地了解这些基因组区域的组织和表达的进化，我们研究了鲨鱼（Scyliorhinus canicula）的 Hox 基因簇。我们从几个胚胎 cDNA 文库中测序了 225,580 个表达序列标签。Blast 搜索鉴定出了几乎所有 HoxA、HoxB 和 HoxD 簇基因的对应转录本。没有鉴定出 HoxC 转录本，这表明该簇缺失或高度退化。使用 Hox 基因序列作为探针，我们从一个覆盖三个基因簇完整区域的细菌人工染色体文库中选择并测序了七个克隆。将 cDNA 映射到这些基因组序列上表明，相邻 Hox 基因之间存在广泛的选择性剪接和未翻译外显子共享。使用序列相似性，我们无法从其他物种的转录本中鉴定出同源的非编码外显子。然而，通过比较不同物种中这些外显子上游保守的非编码序列，我们能够鉴定出一些外显子之间的同源性。一些选择性剪接变体可能非常古老，已经被祖先的 Hox 基因簇编码。我们还鉴定了几个不编码 Hox 蛋白的转录本，可能没有被翻译，除了一个之外，所有转录本都是与 Hox 基因反向的。对鲨鱼 Hox 基因簇转录组的调查表明，在哺乳动物中观察到的高度复杂性是有颌类动物的一个祖先特征。
