Assessing Recent Selection and Functionality at Long Noncoding RNA Loci in the Mouse Genome.
Assessing Recent Selection and Functionality at Long Noncoding RNA Loci in the Mouse Genome.
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DOI：
10.1093/gbe/evv155
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发表时间：
2015-08-12
影响因子：
3.3
通讯作者：
Keightley PD
中科院分区：
文献类型：
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作者：
Wiberg RA;Halligan DL;Ness RW;Necsulea A;Kaessmann H;Keightley PD
长链非编码RNA（longnoncodingRNA，lncRNA）是研究最多的一类非编码元件。关于lncRNA的比例是功能性的还是仅仅代表转录噪音的争论仍在继续。虽然单个lncRNA的表征已经确定了大约200个真核生物的功能位点，但一般调查只发现了少量或没有长期进化保守的证据。虽然这种保守性的缺乏表明大多数lncRNA是无功能的，但仍有可能是一些代表了最近的进化创新。我们研究了最近的选择压力作用于小鼠种群中的lncRNA。我们比较了一组野生家鼠（Mus musculus castaneus）中约10，000个lncRNA位点的种内核苷酸变异模式，以及大鼠（Rattus norvegicus）的种间核苷酸差异。预期在选择性约束下的基因座显示减少的核苷酸多样性和趋异。我们发现有限的证据序列保守性与puperminally进化的祖先重复序列（AR）相比。AR、蛋白质编码（PC）外显子和lncRNA以及相关侧翼区域之间的序列多样性和趋异性的比较显示，与AR相比，lncRNA的序列多样性和趋异性较弱，但显著较低。在脊椎动物生殖系统中保守的lncRNA在物种内的序列多样性低于一般lncRNA。一组74个具有功能特征的lncRNA显示出与PC外显子相当的多样性和分歧水平，表明这些lncRNA受到大量选择性限制。我们的研究结果表明，在小鼠种群中，大多数lncRNA基因座的进化速度与AR相似，而较老的lncRNA往往显示出与PC基因相似的选择信号。
Long noncoding RNAs (lncRNAs) are one of the most intensively studied groups of noncoding elements. Debate continues over what proportion of lncRNAs are functional or merely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains that some represent recent evolutionary innovations. We examine recent selection pressures acting on lncRNAs in mouse populations. We compare patterns of within-species nucleotide variation at approximately 10,000 lncRNA loci in a cohort of the wild house mouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation compared with putatively neutrally evolving ancestral repeats (ARs). Comparisons of sequence diversity and divergence between ARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower within-species sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, in mouse populations, most lncRNA loci evolve at rates similar to ARs, whereas older lncRNAs tend to show signals of selection similar to PC genes.