A bimodal pattern of relatedness between the Salmonella Paratyphi A and Typhi genomes: Convergence or divergence by homologous recombination?

Abstract

All Salmonella can cause disease but severe systemic infections are primarily caused by a few lineages. Paratyphi A and Typhi are the deadliest human restricted serovars, responsible for ∼600,000 deaths per annum. We developed a Bayesian changepoint model that uses variation in the degree of nucleotide divergence along two genomes to detect homologous recombination between these strains, and with other lineages of Salmonella enterica. Paratyphi A and Typhi showed an atypical and surprising pattern. For three quarters of their genomes, they appear to be distantly related members of the species S. enterica, both in their gene content and nucleotide divergence. However, the remaining quarter is much more similar in both aspects, with average nucleotide divergence of 0.18% instead of 1.2%. We describe two different scenarios that could have led to this pattern, convergence and divergence, and conclude that the former is more likely based on a variety of criteria. The convergence scenario implies that, although Paratyphi A and Typhi were not especially close relatives within S. enterica, they have gone through a burst of recombination involving more than 100 recombination events. Several of the recombination events transferred novel genes in addition to homologous sequences, resulting in similar gene content in the two lineages. We propose that recombination between Typhi and Paratyphi A has allowed the exchange of gene variants that are important for their adaptation to their common ecological niche, the human host.