Intragenic DNA inversions expand bacterial coding capacity

Area of Science:

• Microbiology
• Genomics
• Bioinformatics

Background:

• Bacterial populations exhibit heterogeneity, not strict clonality, due to mechanisms like phase variation.
• Phase variation, often mediated by DNA inversions, alters gene expression and impacts bacterial fitness and survival.
• DNA inversions can flip promoter orientations, controlling gene transcription.

Purpose of the Study:

• To develop a computational tool (PhaVa) for identifying DNA inversions in long-read sequencing data.
• To discover and characterize a novel class of DNA inversions, termed 'intragenic invertons', located within genes.

Main Methods:

• Development of the PhaVa computational tool for DNA inversion detection.
• Analysis of long-read sequencing datasets from bacterial and archaeal isolates.
• Experimental validation of identified intragenic invertons in *Bacteroides thetaiotaomicron*.

Main Results:

• Identification of 372 novel intragenic invertons across diverse bacterial and archaeal genomes.
• Demonstration that intragenic invertons enable genes to encode multiple protein variants by flipping internal DNA sequences.
• Experimental validation of ten intragenic invertons and characterization of one in the *thiC* gene.

Conclusions:

• Intragenic invertons represent a significant discovery, expanding the coding capacity of bacterial genomes.
• PhaVa is a valuable tool for identifying DNA inversions, facilitating further research into bacterial genome dynamics.
• This mechanism provides bacteria with a novel strategy for generating protein diversity and adapting to environmental changes.