RT Journal Article SR Electronic T1 Characterization of hairpin loops and cruciforms across 118,065 genomes spanning the tree of life JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.09.29.615628 DO 10.1101/2024.09.29.615628 A1 Chantzi, Nikol A1 Moeckel, Camille A1 Chan, Candace S. Y A1 Nayak, Akshatha A1 Wang, Guliang A1 Mouratidis, Ioannis A1 Chartoumpekis, Dionysios A1 Vasquez, Karen M. A1 Georgakopoulos-Soares, Ilias YR 2024 UL http://biorxiv.org/content/early/2024/09/29/2024.09.29.615628.abstract AB Inverted repeats (IRs) can form alternative DNA secondary structures called hairpins and cruciforms, which have a multitude of functional roles and have been associated with genomic instability. However, their prevalence across diverse organismal genomes remains only partially understood. Here, we examine the prevalence of IRs across 118,065 complete organismal genomes. Our comprehensive analysis across taxonomic subdivisions reveals significant differences in the distribution, frequency, and biophysical properties of perfect IRs among these genomes. We identify a total of 29,589,132 perfect IRs and show a highly variable density across different organisms, with strikingly distinct patterns observed in Viruses, Bacteria, Archaea, and Eukaryota. We report IRs with perfect arms of extreme lengths, which can extend to hundreds of thousands of base pairs. Our findings demonstrate a strong correlation between IR density and genome size, revealing that Viruses and Bacteria possess the highest density, whereas Eukaryota and Archaea exhibit the lowest relative to their genome size. Additionally, the study reveals the enrichment of IRs at transcription start and termination end sites in prokaryotes and Viruses and underscores their potential roles in gene regulation and genome organization. Through a comprehensive overview of the distribution and characteristics of IRs in a wide array of organisms, this largest-scale analysis to date sheds light on the functional significance of inverted repeats, their contribution to genomic instability, and their evolutionary impact across the tree of life.Competing Interest StatementThe authors have declared no competing interest.