ARC Centre of Excellence in Kangaroo Genomics, The University of Melbourne, Melbourne, Victoria 3010, Australia.
BMC Genomics. 2012 Jun 18;13:251. doi: 10.1186/1471-2164-13-251.
The HOX gene clusters are thought to be highly conserved amongst mammals and other vertebrates, but the long non-coding RNAs have only been studied in detail in human and mouse. The sequencing of the kangaroo genome provides an opportunity to use comparative analyses to compare the HOX clusters of a mammal with a distinct body plan to those of other mammals.
Here we report a comparative analysis of HOX gene clusters between an Australian marsupial of the kangaroo family and the eutherians. There was a strikingly high level of conservation of HOX gene sequence and structure and non-protein coding genes including the microRNAs miR-196a, miR-196b, miR-10a and miR-10b and the long non-coding RNAs HOTAIR, HOTAIRM1 and HOXA11AS that play critical roles in regulating gene expression and controlling development. By microRNA deep sequencing and comparative genomic analyses, two conserved microRNAs (miR-10a and miR-10b) were identified and one new candidate microRNA with typical hairpin precursor structure that is expressed in both fibroblasts and testes was found. The prediction of microRNA target analysis showed that several known microRNA targets, such as miR-10, miR-414 and miR-464, were found in the tammar HOX clusters. In addition, several novel and putative miRNAs were identified that originated from elsewhere in the tammar genome and that target the tammar HOXB and HOXD clusters.
This study confirms that the emergence of known long non-coding RNAs in the HOX clusters clearly predate the marsupial-eutherian divergence 160 Ma ago. It also identified a new potentially functional microRNA as well as conserved miRNAs. These non-coding RNAs may participate in the regulation of HOX genes to influence the body plan of this marsupial.
HOX 基因簇被认为在哺乳动物和其他脊椎动物中高度保守，但长链非编码 RNA 仅在人类和小鼠中进行了详细研究。袋鼠基因组的测序为使用比较分析来比较具有独特身体计划的哺乳动物和其他哺乳动物的 HOX 簇提供了机会。
在这里，我们报告了澳大利亚袋鼠科有袋动物和真兽类之间 HOX 基因簇的比较分析。HOX 基因序列和结构以及非蛋白编码基因（包括 microRNA miR-196a、miR-196b、miR-10a 和 miR-10b 以及长链非编码 RNA HOTAIR、HOTAIRM1 和 HOXA11AS）的保守性非常高，这些基因在调节基因表达和控制发育中起着关键作用。通过 microRNA 深度测序和比较基因组分析，鉴定出两个保守的 microRNA（miR-10a 和 miR-10b），并发现了一个新的候选 microRNA，具有典型的发夹前体结构，在成纤维细胞和睾丸中均有表达。microRNA 靶预测分析表明，在 tammar HOX 簇中发现了几个已知的 microRNA 靶标，如 miR-10、miR-414 和 miR-464。此外，还鉴定出几个新的和推定的 microRNA，它们起源于 tammar 基因组的其他地方，靶向 tammar HOXB 和 HOXD 簇。
这项研究证实，已知长链非编码 RNA 在 HOX 簇中的出现显然早于 1.6 亿年前的有袋类和真兽类分化。它还鉴定出一种新的潜在功能 microRNA 以及保守的 microRNA。这些非编码 RNA 可能参与 HOX 基因的调控，影响这种有袋动物的身体计划。
