Non-B DNA and microsatellite variation and evolution

Jan 8, 2018 · 8 min read
project

Credit: Wilfried Guiblet

Approximately 13% of the genome can fold into DNA structures different from the B-form double-helix discovered by Watson and Crick. Such “non-B DNA” structures include cruciforms, triplexes, slipped-strand structures, G-quadruplexes (G4s), Z-DNA, and bent DNA. They form at certain DNA sequence motifs that are ubiquitous in the genomes of prokaryotes and eukaryotes. Non-B structures form intermittently and can be stabilized under certain conditions in the cell. They are emerging as key regulators of many cellular processes (e.g., replication and transcription), which may be sensitive to the environment and to temporal signals associated with cell cycle and development. Non-B DNA also affects mutation rates. Despite their clear importance in the genome, non-B DNA motifs have been critically underexplored, and studying their evolution will bring us closer to deciphering their functions in the cell. Note that many microsatellites form non-B DNA.

Collaborators: Kristin Eckert and Francesca Chiaromonte

Members

Hana Palova Hana Palova Researcher Huiqing Zeng Huiqing Zeng Research Technologist Jacob Sieg Jacob Sieg Postdoctoral Scholar Saswat Kumar Mohanty Saswat Kumar Mohanty Ph.D. Student

Collaborators

Francesca Chiaromonte Francesca Chiaromonte Marzia Cremona Marzia Cremona Visiting Research Professor Yifei Huang Yifei Huang

Press Releases

Beyond the double helix: Alternative DNA conformations in ape genomes

UNIVERSITY PARK, Pa. — Certain DNA sequences can form structures other than the canonical double helix. These alternative DNA conformations — referred to as non-B DNA — have been implicated as regulators of cellular processes and of genome evolution, but their DNA tends to be repetitive, which…

Publications

Saswat Kumar Mohanty, MG Marin, Linnéa Smeds, Francesca Chiaromonte, CD Huber, Kateryna Makova, Ph.D., Human Pangenome Reference Consortium (2026). Variation and selection at predicted G-quadruplexes across the human pangenome. BIORXIV.
Paper Link Non-B DNA & Microsatellite
Kateryna Makova, Ph.D., S Mohanty, Linnéa Smeds, Jacob Sieg, A Lahnsteiner (2026). Unraveling Non-B DNA Structures in the Era of Telomere-to-Telomere Genomes. ANNU REV GENOMICS HUM GENET.
Paper Link Non-B DNA & Microsatellite
G Formenti, N Jain, JA Medico, M Sollitto, D Antipov, S Barcellos, M Biegler, I Borges, JK Chang, Y Chen, H Cheng, H Conceição, M Davenport, L De Oliveira, E Duarte, G Durham, J Fenn, N Forde, PA Galante, K Gerhardt, AM Giani, S Giunta, J Kim, A Komissarov, B Koo, S Koren, D Larkin, C Lee, H Li, K Makova, P Masterson, T Murphy, K McCaffrey, RLV Mercuri, Y Na, MJ O’Connell, S Ou, A Phillippy, M Popova, A Rhie, FJ Ruiz-Ruano, S Secomandi, Linnéa Smeds, A Suh, T Tilley, N Vontzou, PD Waters, J Balacco, ED Jarvis (2026). The complete genome of a songbird. CELL, ACCEPTED.
Paper Link Non-B DNA & Microsatellite
D García-Ruano, M Georges, Saswat Kumar Mohanty, R Baaziz, Kateryna Makova, Ph.D., M Nikolski, D Chalopin (2026). Uncertainty-aware benchmarking reveals ambiguous transcripts in mRNA-lncRNA classification. BIORXIV.
Paper Link Non-B DNA & Microsatellite
Xinru Zhang, S Mohanty, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2026). Substitution spectrum and selection at G-quadruplexes in great ape telomere-to-telomere genomes. GENOME BIOL EVOL.
Paper Link Non-B DNA & Microsatellite
Jacob Sieg, Huiqing Zeng, Hana Palova, Linnéa Smeds, S Mohanty, A Lahnsteiner, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2025). Comparative analysis of single-stranded and non-canonical DNA formation in human and other ape cells with telomere-to-telomere genomes. BIORXIV.
Paper Link Non-B DNA & Microsatellite
Linnéa Smeds, S Secomandi, C Lee, Francesca Chiaromonte, E Jarvis, G Formenti, K Makova (2025). Non-canonical DNA in bird telomere-to-telomere genomes. BIORXIV.
Paper Link Non-B DNA & Microsatellite
Saswat Kumar Mohanty, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2025). Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes. GENOME BIOL.
Paper Link Non-B DNA & Microsatellite
S Hile, Matthias Weissensteiner, K Pytko, J Dahl, E Kejnovský, I Kejnovská, M Hedglin, I Georgakopoulos-Soares, Kateryna Makova, Ph.D., K Eckert (2025). Replicative DNA polymerase Epsilon and Delta holoenzymes show wide ranging inhibition at G-Quadruplexes in the human genome. NUCLEIC ACIDS RES.
Paper Link Non-B DNA & Microsatellite
Linnéa Smeds, Kaivan Kamali, I Kejnovská, E Kejnovský, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2025). Non-canonical DNA in human and other ape telomere-to-telomere genomes. NUCLEIC ACIDS RES.
Paper Link Non-B DNA & Microsatellite
A Lahnsteiner, Sarah J. Carnahan Craig, Kaivan Kamali, Bernadette Weissensteiner, Barb McGrath, A Risch, Kateryna Makova, Ph.D. (2024). In vivo detection of DNA secondary structures using Permanganate/S1 Footprinting with Direct Adapter Ligation and Sequencing (PDAL-Seq). METHODS IN ENZYMOLOGY.
Paper Link Non-B DNA & Microsatellite
Matthias Weissensteiner, Marzia Cremona, Wilfried Guiblet, Nick Stoler, Robert Harris, Monika Cechova (Michalovova), Kristin Eckert, Francesca Chiaromonte, YF Huang, Kateryna Makova, Ph.D. (2023). Accurate sequencing of DNA motifs able to form alternative (non-B) structures. GENOME RES.
Paper Link Non-B DNA & Microsatellite
Kateryna Makova, Ph.D., Matthias Weissensteiner (2023). Noncanonical DNA structures are drivers of genome evolution. TRENDS GENET.
Paper Link Non-B DNA & Microsatellite
ME Stein, A Nusawardhana, Matthias Weissensteiner, M Leed, S Zhang, E Kejnovský, I Kejnovská, Kateryna Makova, Ph.D., Kristin Eckert (2022). Variation in G-quadruplex Sequence and Topology Differentially Impacts Human DNA Polymerase Fidelity. DNA REPAIR.
Paper Link Non-B DNA & Microsatellite
Wilfried Guiblet, Michael DeGiorgio, X Cheng, Francesca Chiaromonte, Kristin Eckert, YF Huang, Kateryna Makova, Ph.D. (2021). Selection and thermostability suggest G-quadruplexes are novel functional elements of the human genome. GENOME RES.
Paper Link Non-B DNA & Microsatellite
Wilfried Guiblet, Marzia Cremona, Robert Harris, Di (Bruce) Chen, Kristin Eckert, Francesca Chiaromonte, Yifei Huang, Kateryna Makova, Ph.D. (2021). Non-B DNA: A major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome. NUCLEIC ACIDS RES.
Paper Link Regional variation Non-B DNA & Microsatellite
Nick Stoler, Barbara Arbeithuber, G Povysil, M Heinzl, R Salazar, Kateryna Makova, Ph.D., I Tiemann-Boege, Anton Nekrutenko (2020). Family reunion via error correction: an efficient analysis of duplex sequencing data. BMC BIOINFORMATICS.
Code Paper Link Mitochondrial Non-B DNA & Microsatellite
Wilfried Guiblet, Marzia Cremona, Monika Cechova (Michalovova), Robert Harris, I Kejnovská, E Kejnovský, Kristin Eckert, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2018). Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate. GENOME RES.
Press Release Paper Link Regional variation Non-B DNA & Microsatellite
Marzia Cremona, A Pini, F Cumbo, Kateryna Makova, Ph.D., Francesca Chiaromonte, S Vantini (2018). IWTomics: testing high-resolution sequence-based `Omics' data at multiple locations and scales. BIOINFORMATICS.
Paper Link Non-B DNA & Microsatellite Regional variation
Arkarachai Fungtammasan, Marta Tomaszkiewicz, Rebeca Campos-Sanchez, Kristin Eckert, Michael DeGiorgio, Kateryna Makova, Ph.D. (2016). Reverse Transcription Errors and RNA–DNA Differences at Short Tandem Repeats. MOL BIOL EVOL.
Paper Link Non-B DNA & Microsatellite
Arkarachai Fungtammasan, Guru Ananda, SE Hile, Marcia Shu-Wei Su, C Sun, Robert Harris, Paul Medvedev, Kristin Eckert, Kateryna Makova, Ph.D. (2015). Accurate typing of short tandem repeats from genome-wide sequencing data and its applications. GENOME RES.
Paper Link Non-B DNA & Microsatellite
Guru Ananda, SE Hile, Amanda Breski, Y Wang, Yogeshwar Kelkar, Kateryna Makova, Ph.D., Kristin Eckert (2014). Microsatellite Interruptions Stabilize Primate Genomes and Exist as Population-Specific Single Nucleotide Polymorphisms within Individual Human Genomes. PLOS GENET.
Paper Link Non-B DNA & Microsatellite
BA Baptiste, Guru Ananda, N Strubczewski, A Lutzkanin, SJ Khoo, A Srikanth, N Kim, Kateryna Makova, Ph.D., MM Krasilnikova, Kristin Eckert (2013). Mature Microsatellites: Mechanisms Underlying Dinucleotide Microsatellite Mutational Biases in Human Cells. G3-GENES GENOM GENET.
Paper Link Non-B DNA & Microsatellite
SB Montgomery, DL Goode, Erika Kvikstad, CA Albers, ZD Zhang, XJ Mu, Guru Ananda, B Howie, KJ Karczewski, KS Smith, V Anaya, R Richardson, J Davis, The 1000 Genomes Project Consortium, DG MacArthur, A Sidow, L Duret, M Gerstein, Kateryna Makova, Ph.D., J Marchini, G McVean, G Lunter (2013). The origin, evolution, and functional impact of short insertion–deletion variants identified in 179 human genomes. GENOME RES.
Paper Link Non-B DNA & Microsatellite
Guru Ananda, E Walsh, KD Jacob, MM Krasilnikova, Kristin Eckert, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2013). Distinct Mutational Behaviors Differentiate Short Tandem Repeats from Microsatellites in the Human Genome. GENOME BIOL EVOL.
Paper Link Non-B DNA & Microsatellite
Arkarachai Fungtammasan, E Walsh, Francesca Chiaromonte, Kristin Eckert, Kateryna Makova, Ph.D. (2012). A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?. GENOME RES.
Paper Link Non-B DNA & Microsatellite Regional variation
Yogeshwar Kelkar, Kristin Eckert, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2011). A matter of life or death: How microsatellites emerge in and vanish from the human genome. GENOME RES.
Paper Link Non-B DNA & Microsatellite
Yogeshwar Kelkar, N Strubczewski, SE Hile, Francesca Chiaromonte, Kristin Eckert, Kateryna Makova, Ph.D. (2010). What Is a Microsatellite: A Computational and Experimental Definition Based upon Repeat Mutational Behavior at A/T and GT/AC Repeats. GENOME BIOL EVOL.
Paper Link Non-B DNA & Microsatellite
Yogeshwar Kelkar, S Tyekucheva, Francesca Chiaromonte, Kateryna Makova, Ph.D. (2008). The genome-wide determinants of human and chimpanzee microsatellite evolution. GENOME RES.
Paper Link Non-B DNA & Microsatellite
JL Longmire, JL Roach, M Maltbie, PS White, OL Tatum, Kateryna Makova, Ph.D., DC Hahn (2003). Tetranucleotide microsatellite markers for the Brown-headed Cowbird Molothrus ater. J AVIAN BIOL.
Paper Link Non-B DNA & Microsatellite
Kateryna Makova, Ph.D., Anton Nekrutenko, RJ Baker (2000). Evolution of Microsatellite Alleles in Four Species of Mice (Genus Apodemus). J MOL EVOL.
Paper Link Non-B DNA & Microsatellite
Anton Nekrutenko, Kateryna Makova, Ph.D., RJ Baker (2000). Isolation of binary species-specific PCR-based markers and their value for diagnostic applications. GENE.
Paper Link Non-B DNA & Microsatellite
Anton Nekrutenko, Kateryna Makova, Ph.D., RK Chesser, RJ Baker (1999). Representational difference analysis to distinguish cryptic species. MOL ECOL.
Paper Link Non-B DNA & Microsatellite
RJ Baker, Kateryna Makova, Ph.D., RK Chesser (1999). Microsatellites indicate a high frequency of multiple paternity in Apodemus (Rodentia). MOL ECOL.
Paper Link Non-B DNA & Microsatellite
(1998). Microsattelite markers in wood mouse and striped field mouse (genus Apodemus). MOL ECOL.
Paper Link Non-B DNA & Microsatellite
Kateryna Makova, Ph.D., JC Patton (1998). Increased Yield of Tri- and Tetranucleotide Heterospecific Microsatellites from Unenriched Small-Insert Libraries. BIOTECHNIQUES.
Paper Link Non-B DNA & Microsatellite