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Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones.

Baddam R, Kumar N, Shaik S, Lankapalli AK, Ahmed N - Sci Rep (2014)

Bottom Line: We observed a decline in core functional gene content and a significant increase in accessory pseudogene content.Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S.Typhi possibly resorts to metabolic fine tuning for its adaptation.

View Article: PubMed Central - PubMed

Affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500046, India.

ABSTRACT
Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study, we analyzed genomes of S. Typhi from different parts of Southeast Asia and Oceania, comprising of isolates from outbreak, sporadic and carrier cases. The genomes showed high genetic relatedness with limited opportunity for gene acquisition as evident from pan-genome structure. Given that pseudogenisation is an active process in S. Typhi, we further investigated core and pan-genome profiles of functional and pseudogenes separately. We observed a decline in core functional gene content and a significant increase in accessory pseudogene content. Upon functional classification, genes encoding metabolic functions formed a major constituent of pseudogenes as well as core functional gene clusters with SNPs. Further, an in-depth analysis of accessory pseudogene content revealed the existence of heterogeneous complements of functional and pseudogenes among the strains. In addition, these polymorphic genes were also enriched in metabolism related functions. Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S. Typhi possibly resorts to metabolic fine tuning for its adaptation.

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Phylogenomic Tree.The whole genome information was used to build the distance matrix using Gegenees. The phylogenetic tree was developed using SplitsTree by NJ method. This revealed close similarity among genomes and also co-clustering of strains isolated from the same regions.
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f1: Phylogenomic Tree.The whole genome information was used to build the distance matrix using Gegenees. The phylogenetic tree was developed using SplitsTree by NJ method. This revealed close similarity among genomes and also co-clustering of strains isolated from the same regions.

Mentions: The whole genome based phylogenetic tree allowed us to understand the close genetic relationship among various strains as shown in Figure 1. The strain BL196 isolated during the outbreak, and the carrier strain CR0044 isolated a year later, co-clustered revealing close similarity. This suggests that the strain CR0044 could have emerged due to clonal expansion of BL196, whereas another carrier strain CR0063 might have accumulated enough variations allowing it to cluster separately. The two strains isolated from Papua New Guinea, UJ816A and UJ308A, also clustered together with respect to all other strains. This observation by whole genome based phylogeny corroborates with the PFGE based analysis of Thong et al, where S. Typhi strains from Papua New Guinea showed highly similar PFGE patterns exhibiting limited genetic diversity among the strains30. As typhoid cases were rarely detected in Papua New Guinea before 1985, the limited observed diversity might be due to clonal expansion of a single ancestral strain30. The strains CT18, P-stx-12, ST0208 have shown up independently in the tree. The close similarity of these genomes is also reflected in whole genome alignment as depicted (Figure 2). This analysis once again reinforces the genetically monomorphic nature of this pathogen and our observations are in concurrence with the previous findings based on Multilocus sequence typing and other techniques1732. A similar co-clustering pattern was also observed with Maximum Likelihood based phylogenetic tree constructed using core gene clusters without paralogs (Supplementary Figure S1).


Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones.

Baddam R, Kumar N, Shaik S, Lankapalli AK, Ahmed N - Sci Rep (2014)

Phylogenomic Tree.The whole genome information was used to build the distance matrix using Gegenees. The phylogenetic tree was developed using SplitsTree by NJ method. This revealed close similarity among genomes and also co-clustering of strains isolated from the same regions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264004&req=5

f1: Phylogenomic Tree.The whole genome information was used to build the distance matrix using Gegenees. The phylogenetic tree was developed using SplitsTree by NJ method. This revealed close similarity among genomes and also co-clustering of strains isolated from the same regions.
Mentions: The whole genome based phylogenetic tree allowed us to understand the close genetic relationship among various strains as shown in Figure 1. The strain BL196 isolated during the outbreak, and the carrier strain CR0044 isolated a year later, co-clustered revealing close similarity. This suggests that the strain CR0044 could have emerged due to clonal expansion of BL196, whereas another carrier strain CR0063 might have accumulated enough variations allowing it to cluster separately. The two strains isolated from Papua New Guinea, UJ816A and UJ308A, also clustered together with respect to all other strains. This observation by whole genome based phylogeny corroborates with the PFGE based analysis of Thong et al, where S. Typhi strains from Papua New Guinea showed highly similar PFGE patterns exhibiting limited genetic diversity among the strains30. As typhoid cases were rarely detected in Papua New Guinea before 1985, the limited observed diversity might be due to clonal expansion of a single ancestral strain30. The strains CT18, P-stx-12, ST0208 have shown up independently in the tree. The close similarity of these genomes is also reflected in whole genome alignment as depicted (Figure 2). This analysis once again reinforces the genetically monomorphic nature of this pathogen and our observations are in concurrence with the previous findings based on Multilocus sequence typing and other techniques1732. A similar co-clustering pattern was also observed with Maximum Likelihood based phylogenetic tree constructed using core gene clusters without paralogs (Supplementary Figure S1).

Bottom Line: We observed a decline in core functional gene content and a significant increase in accessory pseudogene content.Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S.Typhi possibly resorts to metabolic fine tuning for its adaptation.

View Article: PubMed Central - PubMed

Affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500046, India.

ABSTRACT
Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study, we analyzed genomes of S. Typhi from different parts of Southeast Asia and Oceania, comprising of isolates from outbreak, sporadic and carrier cases. The genomes showed high genetic relatedness with limited opportunity for gene acquisition as evident from pan-genome structure. Given that pseudogenisation is an active process in S. Typhi, we further investigated core and pan-genome profiles of functional and pseudogenes separately. We observed a decline in core functional gene content and a significant increase in accessory pseudogene content. Upon functional classification, genes encoding metabolic functions formed a major constituent of pseudogenes as well as core functional gene clusters with SNPs. Further, an in-depth analysis of accessory pseudogene content revealed the existence of heterogeneous complements of functional and pseudogenes among the strains. In addition, these polymorphic genes were also enriched in metabolism related functions. Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S. Typhi possibly resorts to metabolic fine tuning for its adaptation.

Show MeSH
Related in: MedlinePlus