Unraveling Non-B DNA Structures in the Era of Telomere-to-Telomere Genomes
Abstract
Telomere-to-telomere (T2T) genome assemblies now provide a complete representation of genomic sequences, enabling unprecedented exploration of non-B DNA structures—secondary conformations distinct from canonical B-DNA. These fully resolved genomes reveal the true abundance and chromosomal distribution of motifs capable of forming G-quadruplexes, Z-DNA, triplexes, and other noncanonical structures, including within previously inaccessible satellite and repetitive regions. T2T assemblies also illuminate how non-B DNA influences key biological processes such as replication, recombination, chromatin organization, and transcription. Moreover, emerging evidence links non-B DNA structures to genomic instability, mutation hotspots, and disease etiology. Comparative T2T analyses across species are beginning to uncover evolutionary patterns and selection pressures acting on these motifs. Integrating advanced prediction tools, AI-based analyses, and experimental validation promises to clarify the multifaceted roles of non-B DNA in genome function, regulation, and evolution.
Type
Publication
Annual Review of Genomics and Human Genetics
Authors
Professor
Kateryna is interested in genomics, evolution, and human genetics.
Her lab studies mutations using both computational and experimental
approaches. Additional topics of interest include sex chromosome
evolution and genomics of childhood obesity.
Authors
Postdoctoral Scholar
Linnéa’s research in the Makova lab involves investigating selection in non-canonical DNA from primates, especially G4 quadruplexes, using bioinformatics methods. Linnéa worked for 8 years as a bioinformatician in Dr. Hans Ellegren’s lab, developing approaches to study speciation, mutation rate and sex chromosome evolution in birds, before taking on a Ph. D. in evolutionary genetics. Her thesis “Conservation genomics in inbred Scandinavian wolves using bioinformatic methods” involved work on Y chromosome evolution, admixture, genetic load and structural variation.
Authors
Postdoctoral Scholar
Jacob’s current research in Makova Lab uses a combination of experimental and computational approaches to characterize the role of non-canonical DNA secondary structures in primate genomes. Before joining Makova Lab, Jacob studied RNA biochemistry. His Ph.D. thesis work with Dr. Philip Bevilacqua updated thermodynamic models that describe RNA secondary structures to better reflect the cellular environment. His undergraduate thesis work focused on drug targeting RNA thermometers in bacteria.