Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario M5S 3B2, Canada.
Genetics. 2011 Nov;189(3):967-76. doi: 10.1534/genetics.111.132795. Epub 2011 Sep 2.
Mounting evidence points to differences in gene regulation as a major source of phenotypic variation. MicroRNA-mediated post-transcriptional regulation has emerged recently as a key factor controlling gene activity during development. MicroRNA genes are abundant in genomes, acting as managers of gene expression by directing translational repression. Thus, understanding the role of microRNA sequence variation within populations is essential for fully dissecting the origin and maintenance of phenotypic diversity in nature. In this study, we investigate allelic variation at microRNA loci in the nematode Caenorhabditis briggsae, a close relative of C. elegans. Phylogeographic structure in C. briggsae partitions most strains from around the globe into a "temperate" or a "tropical" clade, with a few strains having divergent, geographically restricted genotypes. Remarkably, strains that follow this latitudinal dichotomy also differ in temperature-associated fitness. With this phylogeographic pattern in mind, we examined polymorphisms in 18 miRNAs in a global sample of C. briggsae isolates and tested whether newly isolated strains conform to this phylogeography. Surprisingly, nucleotide diversity is relatively high in this class of gene that generally experiences strong purifying selection. In particular, we find that miRNAs in C. briggsae are substantially more polymorphic than in Arabidopsis thaliana, despite similar background levels of neutral site diversity between the two species. We find that some mutations suggest functional divergence on the basis of requirements for target site recognition and computational prediction of the effects of the polymorphisms on RNA folding. These findings demonstrate the potential for miRNA polymorphisms to contribute to phenotypic variation within a species. Sequences were deposited in GenBank under accession nos. JN251323-JN251744.
越来越多的证据表明，基因调控的差异是表型变异的主要来源。最近，miRNA 介导的转录后调控已成为控制发育过程中基因活性的关键因素。miRNA 基因在基因组中大量存在，通过指导翻译抑制来充当基因表达的管理者。因此，了解群体中 miRNA 序列变异的作用对于充分剖析自然中表型多样性的起源和维持至关重要。在这项研究中，我们研究了秀丽隐杆线虫（Caenorhabditis briggsae）中 miRNA 基因座的等位基因变异，这是秀丽隐杆线虫（C. elegans）的近亲。C. briggsae 的系统地理学结构将来自全球各地的大多数菌株分为“温带”或“热带”分支，少数菌株具有不同的、地理上受限的基因型。值得注意的是，遵循这种纬度二分法的菌株在与温度相关的适应性方面也存在差异。考虑到这种系统地理学模式，我们在全球范围内的 C. briggsae 分离株样本中检查了 18 个 miRNA 的多态性，并测试了新分离的菌株是否符合这种系统地理学结构。令人惊讶的是，在经历强烈净化选择的这一类基因中，核苷酸多样性相对较高。特别是，我们发现 C. briggsae 中的 miRNA 比拟南芥（Arabidopsis thaliana）中的 miRNA 更加多态，尽管这两个物种之间的中性位点多样性背景水平相似。我们发现，一些突变表明基于靶标识别的功能分化的需求和对多态性对 RNA 折叠影响的计算预测。这些发现表明，miRNA 多态性有可能为物种内的表型变异做出贡献。序列已在 GenBank 中以 JN251323-JN251744 登录号提交。
