傷寒病致病菌的研究在學術(shù)界近百年未有定論,。哈爾濱醫(yī)科大學基因組中心采用比較基因組學方法進行研究,，最終證實傷寒病致病細菌是由不同病原體在分別獲得有關遺傳性狀后，各自發(fā)展成致傷寒病的特殊病原體,，而非由同一祖先進化而來,。有關專家認為，這一結(jié)論對傷寒病的基礎性研究將產(chǎn)生重要影響,，近期出版的國際學術(shù)期刊《公共科學圖書館·綜合》（PLoS ONE）上刊發(fā)了該項研究成果,。
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方法進行研究,，具體說來是對丙型副傷寒沙門氏菌RKS4594株測序,，將它與已測序沙門氏菌進行比較。RKS4594包含一個4833080bp的染色體和一個55414bp的質(zhì)粒,。研究者們預測了4640個完整編碼序列和152個假基因,。RKS4594與豬霍亂沙門氏菌有4346個基因相同，但與其他引起人類傷寒病的傷寒沙門氏菌僅有4008個基因相同,。在比較了6株傷寒沙門氏菌共有的3691個基因并據(jù)此建立了種系進化樹之后,，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化樹之一端,，而傷寒沙門氏菌卻居于同一棵進化樹相反一端的枝頭上,，這說明丙型副傷寒沙門氏菌和傷寒沙門氏菌來源于不同的直系祖先，二者在致病特性上的相似是趨同進化的結(jié)果,。
同時,，他們認為，丙型副傷寒沙門氏菌在與人類的共進化過程中,，很可能遭遇巨大的選擇壓力,，因為丙型副傷寒沙門氏菌和豬霍亂沙門氏菌這兩種近緣細菌在一些蛋白質(zhì)的序列上已發(fā)生顯著變化，其變化速率遠遠超過了分子鐘在無選擇壓力下的預期速率,。這一發(fā)現(xiàn)有助于探討病原體與人體共進化過程中的彼此互作方式與機制,，進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,。這些細菌是來自于共同祖先（即分歧進化的產(chǎn)物）還是各自獨立形成的（趨同進化的產(chǎn)物）,，這個問題的澄清對研究傳染病致病因子的起源、進化和控制有著重要的意義,。
對這個問題的探討,，歐美科學家始于20世紀上半葉。但由于方法學的限制以及問題本身的復雜性,，都沒有得出結(jié)論,。本世紀初，英美科學家先后完成了對傷寒沙門氏菌和甲型副傷寒沙門氏菌的全基因組測序,，使本問題的研究有了很大進展,。然而，兩種細菌的比較還是難以給出確切的答案,。出現(xiàn)第三種導致傷寒病的病原菌的測序和與前兩種細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多年懸而未決的問題初步找到了答案,。他們以翔實的實驗數(shù)據(jù)證明,，導致傷寒病的細菌，不是由共同的直接祖先進化而來,，而是各自分別獲得了有關遺傳性狀最后發(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.
