Earlham Institute, Norwich Research Park, Colney Lane, Norwich, NR47UZ, United Kingdom.
University of East Anglia, Norwich Research Park, Norwich, NR47TJ, United Kingdom.
Sci Rep. 2018 Nov 19;8(1):17050. doi: 10.1038/s41598-018-34243-8.
MiRNAs are crucial regulators of gene expression found across both the plant and animal kingdoms. While the number of annotated miRNAs deposited in miRBase has greatly increased in recent years, few studies provided comparative analyses across sets of related species, or investigated the role of miRNAs in the evolution of gene regulation. We generated small RNA libraries across 5 mammalian species (cow, dog, horse, pig and rabbit) from 4 different tissues (brain, heart, kidney and testis). We identified 1676 miRBase and 413 novel miRNAs by manually curating the set of computational predictions obtained from miRCat and miRDeep2. Our dataset spanning five species has enabled us to investigate the molecular mechanisms and selective pressures driving the evolution of miRNAs in mammals. We highlight the important contributions of intronic sequences (366 orthogroups), duplication events (135 orthogroups) and repetitive elements (37 orthogroups) in the emergence of new miRNA loci. We use this framework to estimate the patterns of gains and losses across the phylogeny, and observe high levels of miRNA turnover. Additionally, the identification of lineage-specific losses enables the characterisation of the selective constraints acting on the associated target sites. Compared to the miRBase subset, novel miRNAs tend to be more tissue specific. 20 percent of novel orthogroups are restricted to the brain, and their target repertoires appear to be enriched for neuron activity and differentiation processes. These findings may reflect an important role for young miRNAs in the evolution of brain expression plasticity. Many seed sequences appear to be specific to either the cow or the dog. Analyses on the associated targets highlight the presence of several genes under artificial positive selection, suggesting an involvement of these miRNAs in the domestication process. Altogether, we provide an overview on the evolutionary mechanisms responsible for miRNA turnover in 5 domestic species, and their possible contribution to the evolution of gene regulation.
miRNAs 是在动植物界中都发现的重要基因表达调控因子。尽管近年来在 miRBase 中注释的 miRNA 数量大大增加，但很少有研究对相关物种的 miRNA 进行比较分析，也没有研究 miRNA 在基因调控进化中的作用。我们从 4 种不同的组织（大脑、心脏、肾脏和睾丸）中生成了 5 种哺乳动物（牛、狗、马、猪和兔）的小 RNA 文库。我们通过手动整理从 miRCat 和 miRDeep2 获得的计算预测集合，鉴定了 1676 个 miRBase 和 413 个新 miRNA。我们的数据集跨越了 5 个物种，使我们能够研究推动哺乳动物 miRNA 进化的分子机制和选择压力。我们强调了内含子序列（366 个同源群组）、复制事件（135 个同源群组）和重复元件（37 个同源群组）在新 miRNA 位点出现中的重要贡献。我们利用这个框架来估计整个系统发育中的增益和损失模式，并观察到 miRNA 的高周转率。此外，谱系特异性损失的鉴定使我们能够描述作用于相关靶位点的选择压力。与 miRBase 子集相比，新的 miRNA 往往更具组织特异性。20%的新同源群组仅限于大脑，其靶标库似乎富含神经元活性和分化过程。这些发现可能反映了年轻的 miRNA 在大脑表达可塑性进化中的重要作用。许多种子序列似乎只存在于牛或狗中。对相关靶标的分析强调了一些基因受到人为正选择的存在，这表明这些 miRNA 参与了驯化过程。总的来说，我们提供了一个关于负责 5 个家养物种 miRNA 周转率的进化机制的概述，以及它们对基因调控进化的可能贡献。
