Laboratory of Integrated Biosciences, School of Life Science, Sun Yat-sen University, Guangzhou, China.
Comput Biol Chem. 2010 Aug;34(4):232-41. doi: 10.1016/j.compbiolchem.2010.08.001. Epub 2010 Aug 24.
A number of microRNAs (miRNAs) that are evolutionarily conserved not beyond primate lineage have been identified. These primate-specific miRNAs (ps-miRNAs) may attribute to the difference between high-level primates and non-primate mammals or lower vertebrates. Despite of their importance, the genome-wide miRNA conservation patterns and the properties of these ps-miRNAs are largely elusive. In this study, we developed a robust classification system to assess the conservation pattern of all human mature miRNAs across 44 vertebrate genomes. By this comparative genomic analysis, a novel set of 269 ps-miRNAs were identified. We found that many ps-miRNAs were enriched in chromosome 19 and X, forming two main clusters hereafter referred as C19MC and CXMC, respectively. When comparing the seed of ps-miRNAs themselves or with non-ps-miRNAs, more than one half ps-miRNAs sharing common seeds were belonged to C19MC, 9 of which retained a unique seed that had been reported to be enriched in human embryonic stem cells (hESCs) specific miRNAs. Moreover, the most abundant ps-miRNA common seed was possessed by miR-548 family. Most ps-miRNAs had very low expression in adult tissues, which may be attributed to temporal and spatial specific transcript regulation. The ps-miRNAs with relatively high expression were mainly belonged to C19MC and CXMC, and preferentially expressed in hESCs and reproductive system. Sequence anatomy revealed that C19MC ps-miRNAs were highly conserved but not beyond primates and of great sequence similarity. Gene Ontology and KEGG pathway enrichment analyses of predicted target genes indicated that C19MC ps-miRNAs were strongly associated with developmental processes and various cancers. In conclusion, ps-miRNAs may play critical roles in differentiation and growth regulation during early development, especially in maintaining the pluripotency of hESCs. Results from this study may help explaining the differences between primates and lower vertebrates at genetic level.
已经鉴定出许多在灵长类动物谱系之外没有进化保守的 microRNAs（miRNAs）。这些灵长类动物特异性 miRNAs（ps-miRNAs）可能是高等灵长类动物与非灵长类哺乳动物或低等脊椎动物之间存在差异的原因。尽管它们很重要，但这些 ps-miRNAs 的全基因组 miRNA 保守模式和特性在很大程度上仍难以捉摸。在这项研究中，我们开发了一种稳健的分类系统，用于评估 44 种脊椎动物基因组中所有人类成熟 miRNA 的保守模式。通过这种比较基因组分析，鉴定出了一组新的 269 个 ps-miRNAs。我们发现，许多 ps-miRNAs 在染色体 19 和 X 上富集，形成了两个主要簇，分别称为 C19MC 和 CXMC。当比较 ps-miRNAs 本身的种子或与非 ps-miRNAs 的种子时，属于 C19MC 的超过一半的 ps-miRNAs 共享共同的种子，其中 9 个保留了一个独特的种子，该种子已被报道在人类胚胎干细胞（hESCs）特异性 miRNAs 中富集。此外，最丰富的 ps-miRNA 共同种子由 miR-548 家族拥有。大多数 ps-miRNAs 在成年组织中的表达水平非常低，这可能归因于时间和空间特异性转录调控。表达水平相对较高的 ps-miRNAs 主要属于 C19MC 和 CXMC，并且优先在 hESCs 和生殖系统中表达。序列解剖学表明，C19MC ps-miRNAs 高度保守，但不超过灵长类动物，具有很大的序列相似性。预测靶基因的基因本体论和 KEGG 通路富集分析表明，C19MC ps-miRNAs 与发育过程和各种癌症密切相关。总之，ps-miRNAs 可能在早期发育过程中的分化和生长调节中发挥关键作用，特别是在维持 hESCs 的多能性方面。本研究的结果可能有助于从遗传水平上解释灵长类动物和低等脊椎动物之间的差异。
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