Systematicidentification of gene-altering programmed inversions across the bacterialdomain
Programmedchromosomal inversions allow bacteria to generate intra-population genotypicand functional heterogeneity, a bet-hedging strategy important in changingenvironmental challenges, such as bacteriophages and antibiotic drugs. Someprogrammed inversions modify coding sequences, producing different alleles inseveral gene families, most notably in specificity-determining genes such asphage-tail, outer-membrane receptors and Type I restriction-modificationsystems, where systematic searches revealed cross phylum abundance. Yet, abroad systematic search for gene-altering programmed inversions, not guided bypreviously known gene families, has been absent, and little is known abouttheir prevalence across gene families and their common genomic architectures.Here, scanning for intra-species variation in genomes of over 35,000 species,we develop a predictive model of gene-altering inversions, revealing keyattributes of their genomic architectures, including recombinase-proximity andgene-pseudogene size asymmetry. The model predicted over 1200 gene-alteringloci covering known gene families as well as Type II restriction-modificationsystems previously not characterized for programmed inversions. Publiclyavailable long-read sequencing datasets validated representatives of recurringpredicted inversion-targeted gene families, confirming intra-population geneticheterogeneity, even with multiple co-existing combinatorial variants inmultiple inversion systems. Together, these results reveal gene-alteringprogrammed inversions as a key strategy adopted across the bacterial domain,and highlight inversions of Type II restriction-modification systems as apossible new mechanism for maintaining intra-population heterogeneity.