Baddam Ramani, Kumar Narender, Shaik Sabiha, Lankapalli Aditya Kumar, Ahmed Niyaz
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500046, India.
Sci Rep. 2014 Dec 12;4:7457. doi: 10.1038/srep07457.
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.
伤寒热给东南亚及其他流行国家的医疗系统带来了沉重负担。多项流行病学和基因组学研究认为基因假化是伤寒沙门氏菌进化的主要驱动力，但其实际潜力仍不明确。在本研究中，我们分析了来自东南亚和大洋洲不同地区的伤寒沙门氏菌基因组，包括来自暴发、散发病例和携带者病例的分离株。从泛基因组结构来看，这些基因组显示出高度的遗传相关性，基因获得的机会有限。鉴于基因假化在伤寒沙门氏菌中是一个活跃的过程，我们进一步分别研究了功能基因和假基因的核心基因组和泛基因组图谱。我们观察到核心功能基因含量下降，辅助假基因含量显著增加。经功能分类后，编码代谢功能的基因构成了假基因以及具有单核苷酸多态性的核心功能基因簇的主要成分。此外，对辅助假基因含量的深入分析揭示了菌株间功能基因和假基因的异质互补情况。此外，这些多态性基因在代谢相关功能中也很丰富。因此，该研究突出了人群中具有不同代谢潜力的异质菌株的存在，以及伤寒沙门氏菌可能通过代谢微调来实现适应。
