Kateryna Makova guest seminar: “Non-canonical DNA in the human and ape telomere-to-telomere genomes”

On Tuesday, September 2 at 10:15, a guest seminar on "Non-canonical DNA in the human and ape telomere-to-telomere genomes" will be held in room 218 (Riia 23, Tartu). Seminar is led by Professor Kateryna Makova, Director of the Center for Medical Genomics at Pennsylvania State University (USA).

In addition to the classical DNA right-handed helix (B DNA), 10% of the human genome can fold into non-canonical structures (non-B DNA). They regulate key cellular processes and serve as mutational hotspots, yet their precise detection and evolution have remained elusive due to incomplete genome sequences. Here, we analyze non-B DNA in the recently deciphered telomere-to-telomere (T2T) genomes of humans and great apes.

First, we computationally predict motifs capable of forming non-B DNA. These motifs are enriched at the genomic regions added to T2T assemblies, including repetitive sequences, short arms of acrocentric chromosomes (where they may influence satellite dynamics), and centromeres (where they may contribute to centromere function).

Second, we experimentally validate non-B DNA structure formation using Permanganate/S1 footprinting with Direct Adapter Ligation and sequencing (PDAL-seq). We show that clusters of different non-B DNA motifs–particularly direct repeats, G-quadruplexes (G4s), and Z-DNA–drive single-stranded DNA formation. PDAL-seq signal is enriched at promoters, enhancers, and 5’ UTRs, supporting a regulatory role for non-B DNA.

Third, we investigate the evolution of G4s, identifying thousands of conserved and species-specific pG4s. The conserved pG4s are hypomethylated and linked to regulatory regions, while species-specific pG4s may contribute to adaptation and genome expansion. Thus, non-B DNA is unevenly distributed across ape genomes and might have novel functions in previously inaccessible genomic regions.