McCreight Jey C, Schneider Sean E, Wilburn Damien B, Swanson Willie J
Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2017 Jun 22;12(6):e0176596. doi: 10.1371/journal.pone.0176596. eCollection 2017.
MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny. Hundreds of miRNA were validated, and the number of species with experimentally validated miRNA was tripled. These species include a sister taxon to humans (bonobo) and basal primates (aye-aye, mouse lemur, galago). Consistent with previous studies, we found the seed region and mature miRNA to be highly conserved across primates, with overall structural conservation of the pre-miRNA hairpin. However, there were a number of interesting exceptions, including a seed shift due to structural changes in miR-501. We also identified an increase in the number of miR-320 paralogs throughout primate evolution. Many of these non-conserved miRNA appear to regulate neuronal processes, illustrating the importance of investigating miRNA to learn more about human evolution.
微小RNA在人类基因组中大多数转录本的转录后调控中发挥着重要作用,但其在灵长类谱系中的进化情况在很大程度上尚不明确。一种特定的微小RNA可以有一个到数千个信使RNA靶标,这使得序列上的微小变化或微小RNA的整体结构变化有可能产生深远的表型效应。然而,大多数非人类灵长类微小RNA仅通过与人类基因组的同源性来预测,缺乏实验验证。在本研究中,我们对代表广泛灵长类系统发育的13个物种进行了测序。数百种微小RNA得到了验证,经过实验验证的微小RNA的物种数量增加了两倍。这些物种包括人类的姐妹分类群(倭黑猩猩)和基础灵长类动物(指猴、鼠狐猴、婴猴)。与之前的研究一致,我们发现种子区域和成熟微小RNA在灵长类动物中高度保守,前体微小RNA发夹结构整体保守。然而,也有一些有趣的例外情况,包括由于miR - 501结构变化导致的种子移位。我们还发现在整个灵长类进化过程中,miR - 320旁系同源物的数量有所增加。许多这些不保守的微小RNA似乎调控神经元过程,这说明了研究微小RNA对于深入了解人类进化的重要性。