Profound Non-Randomness in Dinucleotide Arrangements within Ultra-Conserved Non-Coding Elements and the Human Genome

SIMPLE SUMMARY: Our study aims to understand mysterious parts of our DNA, known as ultra-conserved non-coding elements. Found in the genomes of mammals and other vertebrates, these long (300 nucleotides, on average) DNA fragments have remained unchanged for hundreds of millions of years, despite numerous mutations happening within them. We do not yet know the function of these elements, but their extraordinary evolutionary stability could help us devise new approaches to preventing harmful mutations that lead to cancer and genetic disorders. We sought to discover why ultra-conserved non-coding elements are so resistant to change by studying their smaller building blocks, called dinucleotides, which play a crucial role in the shape and structure of DNA. Using a bioinformatics approach, we compared the differences in arrangement of dinucleotides in the ultra-conserved non-coding elements to the rest of the human genome. Our study revealed unique patterns within the ultra-conserved non-coding elements sections that distinguish them from the rest of our genetic code. ABSTRACT: 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.