| Abstract [eng] |
Balancing selection continues to be a captivating target because it sheds more light on how genetic diversity is maintained within populations despite external evolutionary pressures. Aspects of balancing selection are crucial for understanding how populations adapt over time to different environmental conditions, disease pressure, and other selective forces. In the context of the Lithuanian population, the study of balancing selection helps to clarify why certain alleles remain predominant in other populations despite the possible advantages of alternative alleles. This may reveal underlying mechanisms of disease resistance, metabolic adaptations, or other fitness-related traits that are of historical and contemporary importance. In addition, the identification of archaic SNPs that are subject to balancing selection is important as they highlight the contributions of ancient alleles to modern genetic diversity and adaptation. Objective of the research was to identify ancient balancing selection signatures across generations in modern human genomes, employing genetic population statistics and deep learning techniques, while identifying which variants or proteins potentially indicate that balancing selection occurred in ancient times but could continue to influence human species today. Deep learning models displayed great capability of effectively predicting loci under selection for a large pool of samples and by different selection types, namely between neutrality and selection (including positive and balancing selection), balancing selection and incomplete sweep, or negative frequency-dependent selection and overdominance. Overall, out of analyzed SNPs in 175 archaic fragments, the strongest selection signals are pronounced on chromosomes 3, 6, 13, 15, 16, 18, and 22, indicating their possible role in genetic adaptation. SNP-related genes are found to be involved in such processes as signaling, metabolism, transport, structural and maintenance functions. Although the most prominent pathways of influence were found to be related to the immune system or inflammatory responses, few of them are also related to neurodegenerative disorders (PACRG and ADAM12) and (TAFA5 and SLC39A11) with gastro-related disorders. Additionally, one of the most previously researched and explored in different populations, SNP rs9356058 in the PACRG gene, is one of the two important regulatory polymorphisms associated with susceptibility to leprosy. Understanding the role of rs9356058 and similar polymorphisms helps clarify the genetic factors that influence disease susceptibility and resistance, providing insight into how historical pathogen exposure has shaped the immune systems of modern humans. |
