Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Saswat Mohanty
Exhibition Number 80
Abstract
G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. G4s contribute to point mutations and structural variation and thus facilitate genomic instability. They play important roles in regulating replication, transcription, and telomere maintenance, and some of them evolve under purifying selection. Nevertheless, the evolutionary dynamics of G4s has remained underexplored. Here we conducted a comprehensive analysis of predicted G4s (pG4s) in the recently released, telomere-to-telomere (T2T) genomes of human and other great apes—bonobo, chimpanzee, gorilla, Bornean orangutan, and Sumatran orangutan. We annotated tens of thousands of new pG4s in T2T compared to previous ape genome assemblies, including 41,236 in the human genome. Analyzing species alignments, we found approximately one-third of pG4s shared by all apes studied and identified thousands of species– and genus-specific pG4s. pG4s accumulated and diverged at rates consistent with divergence times between the studied species. We observed a significant enrichment and hypomethylation of pG4 shared across species at regulatory regions, including promoters, 5’ and 3’UTRs, and origins of replication, strongly suggesting their formation and functional role in these regions. pG4s shared among great apes displayed lower methylation levels compared to species-specific pG4s, suggesting evolutionary conservation of functional roles of the former. Many species-specific pG4s were located in the repetitive and satellite regions deciphered in the T2T genomes. Our findings illuminate the evolutionary dynamics of G4s, their role in gene regulation, and their potential contribution to species-specific adaptations in great apes, emphasizing the utility of high-resolution T2T genomes in uncovering previously elusive genomic features.
Importance
G-quadruplexes (G4s) are non-canonical DNA structures that can influence genome stability and gene regulation. Although G4s are known to play roles in important cellular processes, their evolutionary history remains largely unexplored. Here, we analyze G4s across the newly completed, high-resolution genomes of humans and other great apes, including chimpanzees, gorillas, and orangutans. We discover tens of thousands of previously unrecognized G4s and find that some are shared among all great apes, while others are specific to certain species. By analyzing their distribution across great ape genomes, we revealed how evolutionary forces shape these structures, balancing conservation and species-specific adaptation. These findings pave the way for further research into G4s’ roles in human health and disease.