Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Mol Biol Evol. 2010 Mar;27(3):671-83. doi: 10.1093/molbev/msp284. Epub 2009 Nov 19.
Micro RNAs (miRNAs) are a class of small regulatory RNAs, which posttranscriptionally repress protein production of the targeted messenger RNAs (mRNAs). Accumulating evidence has suggested lineage-specific miRNAs have contributed to lineage-specific characteristics. However, the birth and death of these miRNAs, particularly in primates, largely remain unexplored. We herein characterized the evolutionary history of a newly discovered miRNA cluster on primate X-chromosome, spanning a approximately 33-kb region in human Xq27.3. The cluster consists of six distinct miRNAs, four of which are compactly organized in a 3-kb region belonging to a phylogenetic group distinct from the other two miRNAs. By comparing the genomic structure of this cluster in human with four other primates (chimpanzee, orangutan, rhesus macaque, and marmoset), we identified several previously uncovered miRNAs in these primates that share orthology with the human miRNAs. We found the entire miRNA cluster was well conserved among primate species but unidentifiable in other mammalian species (including mouse, rat, cat, dog, horse, cow, opossum, and platypus), suggesting that the formation of this cluster was after the primate-rodent split but before the emergence of New-World Monkey (represented by marmoset). Our analysis further revealed complex evolutionary dynamics on this locus, characterized by extensive duplication events. Phylogenetic analysis revealed birth and death of the miRNAs within this region, accompanied by rapid evolution, which highlighted their functional importance. These miRNAs are primarily expressed in primate epididymis, part of the male reproductive system. Our analysis showed that their predicted target mRNAs are significantly enriched for several functional classes relevant to epididymal physiology, such as morphogenesis of epithelium and tube development. Furthermore, several genes controlling sperm maturation and male fertility are confidently predicted to be their targets. Collectively, we argue these miRNAs might play an important role in epididymal morphogenesis and sperm maturation and in establishing primate-specific epididymal characteristics.
微小 RNA（miRNAs）是一类小的调节 RNA，它们在后转录水平上抑制靶向信使 RNA（mRNA）的蛋白质产生。越来越多的证据表明，谱系特异性 miRNAs 有助于谱系特异性特征。然而，这些 miRNAs 的诞生和死亡，特别是在灵长类动物中，在很大程度上仍未得到探索。我们在此描述了在灵长类动物 X 染色体上新发现的 miRNA 簇的进化历史，该簇跨越人类 Xq27.3 上约 33kb 的区域。该簇由六个不同的 miRNAs 组成，其中四个紧密组织在一个属于与其他两个 miRNAs 不同的进化群的 3kb 区域内。通过比较人类、黑猩猩、猩猩、恒河猴和绒猴这四种灵长类动物基因组结构，我们在这些灵长类动物中发现了几个以前未被发现的与人类 miRNA 具有同源性的 miRNA。我们发现，整个 miRNA 簇在灵长类动物中高度保守，但在其他哺乳动物中无法识别（包括老鼠、大鼠、猫、狗、马、牛、负鼠和鸭嘴兽），这表明该簇的形成是在灵长类动物和啮齿动物分化之后，但在新世界猴（以绒猴为代表）出现之前。我们的分析进一步揭示了该基因座上复杂的进化动态，其特征是广泛的复制事件。系统发育分析揭示了该区域内 miRNAs 的诞生和死亡，伴随着快速进化，这突出了它们的功能重要性。这些 miRNAs 主要在灵长类动物的附睾中表达，附睾是雄性生殖系统的一部分。我们的分析表明，它们预测的靶 mRNAs 显著富集了与附睾生理学相关的几个功能类别，如上皮形态发生和管发育。此外，几个控制精子成熟和雄性生育力的基因被准确预测为它们的靶标。总的来说，我们认为这些 miRNAs 可能在附睾形态发生和精子成熟以及建立灵长类动物特有的附睾特征方面发挥重要作用。
