Holt Kathryn E, Thomson Nicholas R, Wain John, Langridge Gemma C, Hasan Rumina, Bhutta Zulfiqar A, Quail Michael A, Norbertczak Halina, Walker Danielle, Simmonds Mark, White Brian, Bason Nathalie, Mungall Karen, Dougan Gordon, Parkhill Julian
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
BMC Genomics. 2009 Jan 21;10:36. doi: 10.1186/1471-2164-10-36.
Of the > 2000 serovars of Salmonella enterica subspecies I, most cause self-limiting gastrointestinal disease in a wide range of mammalian hosts. However, S. enterica serovars Typhi and Paratyphi A are restricted to the human host and cause the similar systemic diseases typhoid and paratyphoid fever. Genome sequence similarity between Paratyphi A and Typhi has been attributed to convergent evolution via relatively recent recombination of a quarter of their genomes. The accumulation of pseudogenes is a key feature of these and other host-adapted pathogens, and overlapping pseudogene complements are evident in Paratyphi A and Typhi.
We report the 4.5 Mbp genome of a clinical isolate of Paratyphi A, strain AKU_12601, completely sequenced using capillary techniques and subsequently checked using Illumina/Solexa resequencing. Comparison with the published genome of Paratyphi A ATCC9150 revealed the two are collinear and highly similar, with 188 single nucleotide polymorphisms and 39 insertions/deletions. A comparative analysis of pseudogene complements of these and two finished Typhi genomes (CT18, Ty2) identified several pseudogenes that had been overlooked in prior genome annotations of one or both serovars, and identified 66 pseudogenes shared between serovars. By determining whether each shared and serovar-specific pseudogene had been recombined between Paratyphi A and Typhi, we found evidence that most pseudogenes have accumulated after the recombination between serovars. We also divided pseudogenes into relative-time groups: ancestral pseudogenes inherited from a common ancestor, pseudogenes recombined between serovars which likely arose between initial divergence and later recombination, serovar-specific pseudogenes arising after recombination but prior to the last evolutionary bottlenecks in each population, and more recent strain-specific pseudogenes.
Recombination and pseudogene-formation have been important mechanisms of genetic convergence between Paratyphi A and Typhi, with most pseudogenes arising independently after extensive recombination between the serovars. The recombination events, along with divergence of and within each serovar, provide a relative time scale for pseudogene-forming mutations, affording rare insights into the progression of functional gene loss associated with host adaptation in Salmonella.
在肠炎沙门氏菌亚种I的2000多个血清型中，大多数在多种哺乳动物宿主中引起自限性胃肠道疾病。然而，伤寒沙门氏菌血清型伤寒杆菌和甲型副伤寒杆菌仅限于人类宿主，并引起类似的全身性疾病伤寒和副伤寒热。甲型副伤寒杆菌和伤寒杆菌之间的基因组序列相似性归因于通过其基因组四分之一的相对近期重组而产生的趋同进化。假基因的积累是这些以及其他宿主适应性病原体的一个关键特征，并且在甲型副伤寒杆菌和伤寒杆菌中明显存在重叠的假基因互补序列。
我们报告了一株甲型副伤寒杆菌临床分离株AKU_12601的4.5 Mbp基因组，该基因组使用毛细管技术进行了全序列测定，随后使用Illumina/Solexa重测序进行了检查。与已发表的甲型副伤寒杆菌ATCC9150基因组进行比较，发现两者是共线且高度相似的，有188个单核苷酸多态性和39个插入/缺失。对这些以及两个已完成测序的伤寒杆菌基因组（CT18、Ty2）的假基因互补序列进行比较分析，发现了一些在先前一个或两个血清型的基因组注释中被忽视的假基因，并鉴定出66个血清型之间共享的假基因。通过确定每个共享的和血清型特异性的假基因是否在甲型副伤寒杆菌和伤寒杆菌之间发生了重组，我们发现有证据表明大多数假基因是在血清型之间重组后积累的。我们还将假基因分为相对时间组：从共同祖先继承的祖先假基因、血清型之间重组产生的假基因（可能出现在初始分化和后期重组之间）、重组后但在每个群体的最后进化瓶颈之前出现的血清型特异性假基因，以及更新的菌株特异性假基因。
重组和假基因形成是甲型副伤寒杆菌和伤寒杆菌之间遗传趋同的重要机制，大多数假基因是在血清型之间广泛重组后独立产生的。这些重组事件，以及每个血清型内部和之间的分化，为假基因形成突变提供了一个相对时间尺度，为深入了解沙门氏菌中与宿主适应性相关的功能基因丢失的进展提供了难得的见解。
