Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand.
Mol Biol Evol. 2018 Jun 1;35(6):1451-1462. doi: 10.1093/molbev/msy046.
Mammalian diversification has coincided with a rapid proliferation of various types of noncoding RNAs, including members of both snRNAs and snoRNAs. The significance of this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as a result of random retrotransposition. Hindering progress in our understanding of such observations is the difficulty in establishing function for the diverse features that have been identified in our own genome. Projects such as ENCODE and FANTOM have revealed a hidden world of genomic expression patterns, as well as a host of other potential indicators of biological function. However, such projects have been criticized, particularly from practitioners in the field of molecular evolution, where many suspect these data provide limited insight into biological function. The molecular evolution community has largely taken a skeptical view, thus it is important to establish tests of function. We use a range of data, including data drawn from ENCODE and FANTOM, to examine the case for function for the recent copy number expansion in mammals of six evolutionarily ancient RNA families involved in splicing and rRNA maturation. We use several criteria to assess evidence for function: conservation of sequence and structure, genomic synteny, evidence for transposition, and evidence for species-specific expression. Applying these criteria, we find that only a minority of loci show strong evidence for function and that, for the majority, we cannot reject the null hypothesis of no function.
哺乳动物的多样化与各种类型的非编码 RNA 的快速增殖同时发生，包括 snRNA 和 snoRNA 的成员。然而，这种扩张的意义仍然不清楚。虽然一些 ncRNA 拷贝数的扩张与功能上可处理的效应有关，但这些事件同样可能是中性的，可能是由于随机的 retrotransposition。阻碍我们对这些观察结果的理解的是，在我们自己的基因组中确定各种特征的功能是困难的。ENCODE 和 FANTOM 等项目揭示了基因组表达模式的隐藏世界，以及许多其他潜在的生物功能指标。然而，这些项目受到了批评，特别是在分子进化领域的从业者中，他们许多人怀疑这些数据对生物功能的了解有限。分子进化界基本上持怀疑态度，因此，建立功能测试非常重要。我们使用了一系列数据，包括来自 ENCODE 和 FANTOM 的数据，来研究在哺乳动物中，参与剪接和 rRNA 成熟的六个进化古老的 RNA 家族的最近的拷贝数扩张的功能案例。我们使用了几个标准来评估功能的证据：序列和结构的保守性、基因组同线性、转位的证据和物种特异性表达的证据。应用这些标准，我们发现只有少数基因座具有强烈的功能证据，而对于大多数基因座，我们不能拒绝没有功能的零假设。
