ABSTRACT
Thousands of prolonged sequences of human ultra-conserved non-coding elements (UCNEs) share only one common feature: peculiarities in the unique composition of their dinucleotides. Here we investigate whether the numerous weak signals emanating from these dinucleotide arrangements can be used for computational identification of UCNEs within the human genome. For this purpose, we analyzed 4272 UCNE sequences, encompassing 1 393 448 nucleotides, alongside equally sized control samples of randomly selected human genomic sequences. Our research identified nine different features of dinucleotide arrangements that enable differentiation of UCNEs from the rest of the genome. We employed these nine features, implementing three Machine Learning techniques - Support Vector Machine, Random Forest, and Artificial Neural Networks - to classify UCNEs, achieving an accuracy rate of 82-84%, with specific conditions allowing for over 90% accuracy. Notably, the strongest feature for UCNE identification was the frequency ratio between GpC dinucleotides and the sum of GpG and CpC dinucleotides. Additionally, we investigated the entire pool of 31 046 SNPs located within UCNEs for their representation in the ClinVar database, which catalogs human SNPs with known phenotypic effects. The presence of UCNE-associated SNPs in ClinVar aligns with the expectation of a random distribution, emphasizing the enigmatic nature of UCNE phenotypic manifestation.
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.
ABSTRACT
Sperm cells are transcriptionally and translationally silent. Therefore, they may use one of the remaining mechanisms to respond to stimuli in their environment, the post-translational modification of their proteins. Here we examined three post-translational modifications, acetylation, glutamylation, and glycylation of the protein tubulin in human and cattle sperm. Tubulin is the monomer that makes up microtubules, and microtubules constitute the core component of both the sperm centrioles and the axoneme. We found that the sperm of both species were labeled by antibodies against acetylated tubulin and glutamylated tubulin.
