Evolutionary Analyses of Base-Pairing Interactions in DNA and RNA Secondary Structures
Evolutionary Analyses of Base-Pairing Interactions in DNA and RNA Secondary Structures
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DOI：
10.1093/molbev/msz243
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发表时间：
2020-02-01
影响因子：
10.7
通讯作者：
Hein, Jotun
中科院分区：
文献类型：
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作者：
Golden, Michael;Murrell, Benjamin;Hein, Jotun
功能核酸二级结构内的核苷酸对通常显示与碱基配对的维持一致的共同进化的证据。在这里，我们介绍了一个序列进化模型，MESSI（模拟二级结构相互作用的演变），推断与DNA或RNA序列比对中的碱基配对位点相关的协同进化。MESSI可以估计协同进化，同时考虑未知的二级结构。MESSI还可以使用图形处理单元并行性来提高计算速度。我们使用MESSI来推断非编码RNA比对以及单链RNA和DNA病毒比对中与GC、Au（DNA中的AT）、GU（DNA中的GT）对相关的协同进化。在单链RNA病毒和非编码RNA的碱基配对位点上，GU对协同进化的估计值高于单链DNA病毒中GT对协同进化的估计值。一个潜在的生物物理学解释是GT对不稳定DNA二级结构相同的程度，GU对在RNA中。此外，MESSI还估计比对中各个碱基配对位点的协同进化程度。这些估计值是针对SHAPE-MaP确定的HIV-1 NL 4 -3 RNA二级结构计算的。我们发现，估计协同进化更强烈地与实验确定的SHAPE-地图配对分数比三个非进化措施的碱基配对协变。为了帮助研究人员优先考虑具有潜在功能的子结构，MESSI自动根据子结构内碱基配对位点的共同进化程度对子结构进行排名。这样的排名是为HIV-1亚型B比对创建的，揭示了在几个未表征的顶级亚结构中，先前已被鉴定为具有结构相关功能重要性的顶级亚结构的过量。
Pairs of nucleotides within functional nucleic acid secondary structures often display evidence of coevolution that is consistent with the maintenance of base-pairing. Here, we introduce a sequence evolution model, MESSI (Modeling the Evolution of Secondary Structure Interactions), that infers coevolution associated with base-paired sites in DNA or RNA sequence alignments. MESSI can estimate coevolution while accounting for an unknown secondary structure. MESSI can also use graphics processing unit parallelism to increase computational speed. We used MESSI to infer coevolution associated with GC, AU (AT in DNA), GU (GT in DNA) pairs in noncoding RNA alignments, and in single-stranded RNA and DNA virus alignments. Estimates of GU pair coevolution were found to be higher at base-paired sites in single-stranded RNA viruses and noncoding RNAs than estimates of GT pair coevolution in single-stranded DNA viruses. A potential biophysical explanation is that GT pairs do not stabilize DNA secondary structures to the same extent that GU pairs do in RNA. Additionally, MESSI estimates the degrees of coevolution at individual base-paired sites in an alignment. These estimates were computed for a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure. We found that estimates of coevolution were more strongly correlated with experimentally determined SHAPE-MaP pairing scores than three nonevolutionary measures of base-pairing covariation. To assist researchers in prioritizing substructures with potential functionality, MESSI automatically ranks substructures by degrees of coevolution at base-paired sites within them. Such a ranking was created for an HIV-1 subtype B alignment, revealing an excess of top-ranking substructures that have been previously identified as having structure-related functional importance, among several uncharacterized top-ranking substructures.