傷寒病致病菌的研究在學(xué)術(shù)界近百年未有定論,。哈爾濱醫(yī)科大學(xué)基因組中心采用比較基因組學(xué)方法進(jìn)行研究，最終證實(shí)傷寒病致病細(xì)菌是由不同病原體在分別獲得有關(guān)遺傳性狀后,，各自發(fā)展成致傷寒病的特殊病原體,，而非由同一祖先進(jìn)化而來(lái)。有關(guān)專家認(rèn)為,，這一結(jié)論對(duì)傷寒病的基礎(chǔ)性研究將產(chǎn)生重要影響,，近期出版的國(guó)際學(xué)術(shù)期刊《公共科學(xué)圖書館·綜合》（PLoS ONE）上刊發(fā)了該項(xiàng)研究成果。
據(jù)哈醫(yī)大基因組中心主任劉樹林教授介紹,，課題組采用比較基因組學(xué)方法進(jìn)行研究,，具體說(shuō)來(lái)是對(duì)丙型副傷寒沙門氏菌RKS4594株測(cè)序，將它與已測(cè)序沙門氏菌進(jìn)行比較,。RKS4594包含一個(gè)4833080bp的染色體和一個(gè)55414bp的質(zhì)粒,。研究者們預(yù)測(cè)了4640個(gè)完整編碼序列和152個(gè)假基因。RKS4594與豬霍亂沙門氏菌有4346個(gè)基因相同,，但與其他引起人類傷寒病的傷寒沙門氏菌僅有4008個(gè)基因相同,。在比較了6株傷寒沙門氏菌共有的3691個(gè)基因并據(jù)此建立了種系進(jìn)化樹之后，研究人員發(fā)現(xiàn),，丙型副傷寒沙門氏菌與豬霍亂沙門氏菌共居于進(jìn)化樹之一端,，而傷寒沙門氏菌卻居于同一棵進(jìn)化樹相反一端的枝頭上，這說(shuō)明丙型副傷寒沙門氏菌和傷寒沙門氏菌來(lái)源于不同的直系祖先,，二者在致病特性上的相似是趨同進(jìn)化的結(jié)果,。
同時(shí)，他們認(rèn)為,，丙型副傷寒沙門氏菌在與人類的共進(jìn)化過(guò)程中,，很可能遭遇巨大的選擇壓力，因?yàn)楸透眰抽T氏菌和豬霍亂沙門氏菌這兩種近緣細(xì)菌在一些蛋白質(zhì)的序列上已發(fā)生顯著變化,，其變化速率遠(yuǎn)遠(yuǎn)超過(guò)了分子鐘在無(wú)選擇壓力下的預(yù)期速率,。這一發(fā)現(xiàn)有助于探討病原體與人體共進(jìn)化過(guò)程中的彼此互作方式與機(jī)制,，進(jìn)而有助于尋找人類控制病原體的新手段,。
據(jù)劉樹林介紹，1881年人類首次從傷寒病人身上分離到傷寒沙門氏菌，并確定其為傷寒病的致病菌,。后來(lái)又陸續(xù)分離到另外一些能引起類似疾病的沙門氏菌,，包括甲型副傷寒沙門氏菌和丙型副傷寒沙門氏菌等。這些細(xì)菌是來(lái)自于共同祖先（即分歧進(jìn)化的產(chǎn)物）還是各自獨(dú)立形成的（趨同進(jìn)化的產(chǎn)物）,，這個(gè)問(wèn)題的澄清對(duì)研究傳染病致病因子的起源,、進(jìn)化和控制有著重要的意義。
對(duì)這個(gè)問(wèn)題的探討,，歐美科學(xué)家始于20世紀(jì)上半葉,。但由于方法學(xué)的限制以及問(wèn)題本身的復(fù)雜性，都沒(méi)有得出結(jié)論,。本世紀(jì)初,，英美科學(xué)家先后完成了對(duì)傷寒沙門氏菌和甲型副傷寒沙門氏菌的全基因組測(cè)序，使本問(wèn)題的研究有了很大進(jìn)展,。然而,，兩種細(xì)菌的比較還是難以給出確切的答案。出現(xiàn)第三種導(dǎo)致傷寒病的病原菌的測(cè)序和與前兩種細(xì)菌的綜合分析就顯得十分迫切,。
現(xiàn)在,，哈醫(yī)大的科研人員終于為這個(gè)多年懸而未決的問(wèn)題初步找到了答案。他們以翔實(shí)的實(shí)驗(yàn)數(shù)據(jù)證明,，導(dǎo)致傷寒病的細(xì)菌,，不是由共同的直接祖先進(jìn)化而來(lái)，而是各自分別獲得了有關(guān)遺傳性狀最后發(fā)展成侵襲人體并造成傷寒病的特殊病原體,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 4(2): e4510. doi:10.1371/journal.pone.0004510
Salmonella paratyphi C: Genetic Divergence from Salmonella choleraesuis and Pathogenic Convergence with Salmonella typhi
Wei-Qiao Liu1,2#, Ye Feng3,4#, Yan Wang2#¤a, Qing-Hua Zou5, Fang Chen5, Ji-Tao Guo5, Yi-Hong Peng5, Yan Jin2¤b, Yong-Guo Li6, Song-Nian Hu3,4, Randal N. Johnston7, Gui-Rong Liu1,2,5*, Shu-Lin Liu1,2,5,6*
1 Genomics Research Center, Harbin Medical University, Harbin, China, 2 Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada, 3 JD Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, China, 4 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China, 5 Department of Microbiology, Peking University Health Science Center, Beijing, China, 6 Depatment of Infectious Diseases, First Hospital, Harbin Medical University, Harbin, China, 7 Departments of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada
Background
Although over 1400 Salmonella serovars cause usually self-limited gastroenteritis in humans, a few, e.g., Salmonella typhi and S. paratyphi C, cause typhoid, a potentially fatal systemic infection. It is not known whether the typhoid agents have evolved from a common ancestor (by divergent processes) or acquired similar pathogenic traits independently (by convergent processes). Comparison of different typhoid agents with non-typhoidal Salmonella lineages will provide excellent models for studies on how similar pathogens might have evolved.
Methodologies/Principal Findings
We sequenced a strain of S. paratyphi C, RKS4594, and compared it with previously sequenced Salmonella strains. RKS4594 contains a chromosome of 4,833,080 bp and a plasmid of 55,414 bp. We predicted 4,640 intact coding sequences (4,578 in the chromosome and 62 in the plasmid) and 152 pseudogenes (149 in the chromosome and 3 in the plasmid). RKS4594 shares as many as 4346 of the 4,640 genes with a strain of S. choleraesuis, which is primarily a swine pathogen, but only 4008 genes with another human-adapted typhoid agent, S. typhi. Comparison of 3691 genes shared by all six sequenced Salmonella strains placed S. paratyphi C and S. choleraesuis together at one end, and S. typhi at the opposite end, of the phylogenetic tree, demonstrating separate ancestries of the human-adapted typhoid agents. S. paratyphi C seemed to have suffered enormous selection pressures during its adaptation to man as suggested by the differential nucleotide substitutions and different sets of pseudogenes, between S. paratyphi C and S. choleraesuis.
Conclusions
S. paratyphi C does not share a common ancestor with other human-adapted typhoid agents, supporting the convergent evolution model of the typhoid agents. S. paratyphi C has diverged from a common ancestor with S. choleraesuis by accumulating genomic novelty during adaptation to man.
