Non-B DNA and microsatellite variation and evolution

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

Computational Scientist

Ph.D. student

Ph.D. student

Collaborators

Visiting Research Professor

Publications

. In vivo detection of DNA secondary structures using Permanganate/S1 Footprinting with Direct Adapter Ligation and Sequencing (PDAL-Seq). Methods in Enzymology, Volume 695, Chapter 8, 2024.

Non-B DNA & Microsatellite Paper Link

. Accurate sequencing of DNA motifs able to form alternative (non-B) structures. GENOME RES, 2023.

Non-B DNA & Microsatellite Paper Link

. Variation in G-quadruplex Sequence and Topology Differentially Impacts Human DNA Polymerase Fidelity. DNA REPAIR, 2022.

Non-B DNA & Microsatellite Paper Link

. Selection and thermostability suggest G-quadruplexes are novel functional elements of the human genome. GENOME RES, 2021.

Non-B DNA & Microsatellite Paper Link

. Family reunion via error correction: an efficient analysis of duplex sequencing data. BMC BIOINFORMATICS, 2020.

Code Mitochondrial Non-B DNA & Microsatellite Paper Link

. Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate. GENOME RES, 2018.

Regional variation Non-B DNA & Microsatellite Paper Link Press Release

. Reverse Transcription Errors and RNA–DNA Differences at Short Tandem Repeats. MOL BIOL EVOL, 2016.

Non-B DNA & Microsatellite Paper Link

. Accurate typing of short tandem repeats from genome-wide sequencing data and its applications. GENOME RES, 2015.

Non-B DNA & Microsatellite Paper Link

. Mature Microsatellites: Mechanisms Underlying Dinucleotide Microsatellite Mutational Biases in Human Cells. G3-GENES GENOM GENET, 2013.

Non-B DNA & Microsatellite Paper Link

. Distinct Mutational Behaviors Differentiate Short Tandem Repeats from Microsatellites in the Human Genome. GENOME BIOL EVOL, 2013.

Non-B DNA & Microsatellite Paper Link

. The origin, evolution, and functional impact of short insertion–deletion variants identified in 179 human genomes. GENOME RES, 2013.

Non-B DNA & Microsatellite Paper Link

. Tetranucleotide microsatellite markers for the Brown-headed Cowbird Molothrus ater. J AVIAN BIOL, 2003.

Non-B DNA & Microsatellite Paper Link