Intragenic DNA inversions expand bacterial coding capacity

• Published in: Nature (London) Vol. 634; no. 8032; pp. 234 - 242
• Main Authors: Chanin, Rachael B., West, Patrick T., Wirbel, Jakob, Gill, Matthew O., Green, Gabriella Z. M., Park, Ryan M., Enright, Nora, Miklos, Arjun M., Hickey, Angela S., Brooks, Erin F., Lum, Krystal K., Cristea, Ileana M., Bhatt, Ami S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.10.2024; Nature Publishing Group
• Subjects: 45; 45/91; 631/114/2785; 631/208/325/1996; 631/326/325/1506; 82/58; Amino acid sequence; Bacteria; Bacteroides - genetics; Biosynthesis; Datasets; Datasets as Topic; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA, Bacterial - genetics; Enzymes; Gene expression; Gene Expression Regulation, Bacterial; Genes; Genes, Archaeal - genetics; Genes, Bacterial - genetics; Genetic engineering; Genetic Fitness - genetics; Genome, Archaeal - genetics; Genome, Bacterial - genetics; Genomes; Heterogeneity; Humanities and Social Sciences; Inversions; Laboratories; Mitochondrial DNA; multidisciplinary; Mutation; Nucleotide sequence; Open Reading Frames - genetics; Phase variations; Phenotypic variations; Promoter Regions, Genetic - genetics; Protein biosynthesis; Proteins; Reproducibility of Results; Science; Science (multidisciplinary); Sequence Analysis, DNA; Sequence Inversion - genetics; Software; Subgroups; Thiamine; Thiamine - biosynthesis
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-024-07970-4

Bacterial populations that originate from a single bacterium are not strictly clonal and often contain subgroups with distinct phenotypes 1 . Bacteria can generate heterogeneity through phase variation—a preprogrammed, reversible mechanism that alters gene expression levels across a population 1 . One well-studied type of phase variation involves enzyme-mediated inversion of specific regions of genomic DNA 2 . Frequently, these DNA inversions flip the orientation of promoters, turning transcription of adjacent coding regions on or off 2 . Through this mechanism, inversion can affect fitness, survival or group dynamics 3 , 4 . Here, we describe the development of PhaVa, a computational tool that identifies DNA inversions using long-read datasets. We also identify 372 ‘intragenic invertons’, a novel class of DNA inversions found entirely within genes, in genomes of bacterial and archaeal isolates. Intragenic invertons allow a gene to encode two or more versions of a protein by flipping a DNA sequence within the coding region, thereby increasing coding capacity without increasing genome size. We validate ten intragenic invertons in the gut commensal Bacteroides thetaiotaomicron , and experimentally characterize an intragenic inverton in the thiamine biosynthesis gene thiC . Reversible DNA inversions found entirely within genes enable increased coding capacity by encoding multiple versions of a protein in bacteria and archaea.