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. 2007 Jan;17(1):61-8.
doi: 10.1101/gr.5512906. Epub 2006 Nov 7.

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

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

Xavier Didelot et al. Genome Res. 2007 Jan.

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 approximately 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.

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Figures

Figure 1.
Figure 1.
Gene-by-gene divergence levels between pairs of genomes of Salmonella enterica. The histograms show the distribution of divergence levels for each gene as estimated by the changepoint model. The intensity of green is proportional to the divergence level up to 2% and is used in Figure 2. Pairwise comparisons, showing respectively unrelated S. enterica genomes excluding Typhi or Paratyphi A (A), the same genomes with Typhi and Paratyphi A (B) and of the closely related Enteritidis and Gallinarum genomes (C). The Typhi versus Paratyphi A comparison showing all genes (D) and homologous transposase genes (E), rare genes (F), and phage genes (G).
Figure 2.
Figure 2.
Divergeome of Typhi in comparison with Paratyphi A. The Typhi genome is shown in 32 lines of 150 kb each and one line of 9037 bp. The starting point is as published in Parkhill et al. (2001). Each gene is color-coded by divergence level in green, as in Figure 1D. Regions where Paratyphi A does not align are shown in white. The low-divergence regions are indicated by a red line. Phage genes are shown in orange, transposase genes in blue, and rare genes in gray. Genes for which Typhi is <0.3% diverged at the nucleotide level to one of the seven test genomes are shown as white boxes with black frames. A full list of genes and their positions is shown in Supplemental Table S4. An equivalent divergeome for Paratyphi A is shown in Supplemental Fig. S2.
Figure 3.
Figure 3.
Histogram of the number of rare genes (as defined in the main text) shared by Typhi CT18 and other strains of S. enterica. The arrow at 120 shows the number of genes shared between Typhi and Paratyphi A while the arrow at 55 shows the projected number of genes if the whole genome had the same frequency of rare genes as the high-divergence regions. Note that we have excluded the large SPI7 region, which is shared between Typhi and a handful of other strains. The data is from Porwollik et al. (2004).
Figure 4.
Figure 4.
Scenarios for the divergence of Typhi and Paratyphi A. The trees indicate the clonal history and the arrows indicate genetic exchange events. (A) Illustration of the two scenarios that can explain the bimodal distribution of divergence levels (Fig. 1D). (B) Illustration of the two convergence factors. Under neutral convergence, the two lineages converge due to an elevated rate of exchange between them. Under adaptive convergence, exchanges between the two lineages are preferentially fixed because they contain alleles (gray dots), which confer a selective advantage in their common niche.
Figure 5.
Figure 5.
Properties of low- and high-divergence regions in Typhi vs. Paratyphi A, compared with genomes simulated according to convergence and divergence scenarios.

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