{"title":"Mechanical causes and implications of repetitive DNA motifs.","authors":"Paul Torrillo, David Swigon","doi":"10.1016/j.mbs.2024.109343","DOIUrl":null,"url":null,"abstract":"<p><p>Experimental research suggests that local patterns in DNA sequences can result in stiffer or more curved structures, potentially impacting chromatin formation, transcription regulation, and other processes. However, the effect of sequence variation on DNA geometry and mechanics remains relatively underexplored. Using rigid base pair models to aid rapid computation, we investigated the sample space of 100 bp DNA sequences to identify mechanical extrema based on metrics such as static persistence length, global bend, or angular deviation. Our results show that repetitive DNA motifs are overrepresented in these extrema. We identified specific extremal motifs and demonstrated that their geometric and mechanical properties significantly differ from standard DNA through hierarchical clustering. We provide a mathematical argument supporting the presence of DNA repeats in extremizing sequences. Finally, we find that repetitive DNA motifs with extreme mechanical properties are prevalent in genetic databases and hypothesize that their unique mechanical properties could contribute to this abundance.</p>","PeriodicalId":94129,"journal":{"name":"Mathematical biosciences","volume":" ","pages":"109343"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mathematical biosciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.mbs.2024.109343","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Experimental research suggests that local patterns in DNA sequences can result in stiffer or more curved structures, potentially impacting chromatin formation, transcription regulation, and other processes. However, the effect of sequence variation on DNA geometry and mechanics remains relatively underexplored. Using rigid base pair models to aid rapid computation, we investigated the sample space of 100 bp DNA sequences to identify mechanical extrema based on metrics such as static persistence length, global bend, or angular deviation. Our results show that repetitive DNA motifs are overrepresented in these extrema. We identified specific extremal motifs and demonstrated that their geometric and mechanical properties significantly differ from standard DNA through hierarchical clustering. We provide a mathematical argument supporting the presence of DNA repeats in extremizing sequences. Finally, we find that repetitive DNA motifs with extreme mechanical properties are prevalent in genetic databases and hypothesize that their unique mechanical properties could contribute to this abundance.
实验研究表明,DNA 序列的局部模式可导致结构更坚硬或更弯曲,从而对染色质形成、转录调控和其他过程产生潜在影响。然而,序列变异对 DNA 几何学和力学的影响仍然相对缺乏探索。利用刚性碱基对模型帮助快速计算,我们研究了 100 bp DNA 序列的样本空间,根据静态持续长度、全局弯曲度或角度偏差等指标确定力学极值。我们的研究结果表明,重复的 DNA 主题在这些极值中的比例过高。我们确定了特定的极值图案,并通过分层聚类证明它们的几何和机械特性与标准 DNA 有显著不同。我们提供了支持极端化序列中存在 DNA 重复的数学论据。最后,我们发现具有极端机械特性的重复 DNA 主题在基因数据库中非常普遍,并假设它们独特的机械特性可能是造成这种现象的原因。