(253b) Mutational Correlation Functions Reveal Patterns of Homologous Recombination across the Bacterial Pangenome

Recombination plays a key role in microbial evolution, and is involved in the spread of antibiotic resistance, antigenic variation, and adaptation to the host niche. However, for many bacteria recombination is so pervasive that it obfuscates clonal relationships, creating challenges for inferring the basic parameters of this critical process from real-world data using traditional phylogenetic methods. We recently developed a non-phylogenetic approach that circumvents these obstacles by analyzing and predicting patterns of correlated mutations in bacterial genomes. By calculating analytical solutions for mutational correlation functions using coalescent theory, and fitting these to measurements from large scale sequencing datasets, we accurately infer the parameters of homologous recombination. Remarkably, the theory allows us to fully characterize the impact of recombination in both an observed sample of sequences and the much larger, unobserved genetic pool with which it recombines. Here, we use this approach to quantify variation in homologous recombination across core and accessory genes (essential genes present in all strains of a given species and niche-adaptive genes present in subsets of strains, respectively). Frequent gene gain and loss confounds phylogenetic analysis of accessory genes, and it has remained unclear if core genes have comparatively higher homologous recombination rates, which could change our fundamental understanding of phylogeny. By analyzing 12 bacterial species using >100,000 genomes, we show that core genes often have higher homologous recombination rates than accessory genes. Moreover, we demonstrate that decreased sequence divergence lowers the recombination barrier for the core genome. Homologous recombination may therefore act concomitantly with purifying selection to optimize genes required for essential cellular function. Our work has far-reaching implications for understanding how the interplay between environmental stress and homologous recombination shapes niche-adaptive genes such as those involved with drug-resistance and antigenic variation.