Fedorova Larisa, Crossley Emily R, Mulyar Oleh A, Qiu Shuhao, Freeman Ryan, Fedorov Alexei
CRI Genetics LLC, Santa Monica, CA 90404, USA.
Program of Bioinformatics and Proteomics/Genomics, University of Toledo, Toledo, OH 43606, USA.
Biology (Basel). 2023 Aug 12;12(8):1125. doi: 10.3390/biology12081125.
Long human ultra-conserved non-coding elements (UCNEs) do not have any sequence similarity to each other or other characteristics that make them unalterable during vertebrate evolution. We hypothesized that UCNEs have unique dinucleotide (DN) composition and arrangements compared to the rest of the genome. A total of 4272 human UCNE sequences were analyzed computationally and compared with the whole genomes of human, chicken, zebrafish, and fly. Statistical analysis was performed to assess the non-randomness in DN spacing arrangements within the entire human genome and within UCNEs. Significant non-randomness in DN spacing arrangements was observed in the entire human genome. Additionally, UCNEs exhibited distinct patterns in DN arrangements compared to the rest of the genome. Approximately 83% of all DN pairs within UCNEs showed significant (>10%) non-random genomic arrangements at short distances (2-6 nucleotides) relative to each other. At the extremes, non-randomness in DN spacing distances deviated up to 40% from expected values and were frequently associated with GpC, CpG, ApT, and GpG/CpC dinucleotides. The described peculiarities in DN arrangements have persisted for hundreds of millions of years in vertebrates. These distinctive patterns may suggest that UCNEs have specific DNA conformations.
长人类超保守非编码元件（UCNEs）彼此之间没有任何序列相似性，也没有其他使其在脊椎动物进化过程中不可改变的特征。我们推测，与基因组的其他部分相比，UCNEs具有独特的二核苷酸（DN）组成和排列。对总共4272个人类UCNE序列进行了计算分析，并与人类、鸡、斑马鱼和果蝇的全基因组进行了比较。进行统计分析以评估整个人类基因组和UCNEs内DN间隔排列的非随机性。在整个人类基因组中观察到DN间隔排列存在显著的非随机性。此外，与基因组的其他部分相比，UCNEs在DN排列上表现出独特的模式。UCNEs内所有DN对中约83%在彼此相对较短的距离（2 - 6个核苷酸）处显示出显著（>10%）的非随机基因组排列。在极端情况下，DN间隔距离的非随机性与预期值偏差高达40%，并且经常与GpC、CpG、ApT和GpG/CpC二核苷酸相关。所描述的DN排列的特殊性在脊椎动物中已经存在了数亿年。这些独特的模式可能表明UCNEs具有特定的DNA构象。
