來自軍事醫(yī)學(xué)科學(xué)院微生物流行病研究所,、華大基因研究所,、倫敦大學(xué)學(xué)院等研究機構(gòu)的研究人員發(fā)表了題為“Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis”的研究論文，解析了鼠疫耶爾森氏菌（Yersinia pestis）突變率的歷史演變,。相關(guān)成果發(fā)布在《美國科學(xué)院院刊》（PNAS）上,。
軍事醫(yī)學(xué)科學(xué)院微生物流行病研究所楊瑞馥研究員和宋亞軍博士,、華大基因研究所的王俊博士，以及倫敦大學(xué)學(xué)院的Francois Balloux是這篇論文的共同通訊作者,。
鼠疫（plague）是鼠疫桿菌借鼠蚤傳播為主的烈性傳染病系廣泛流行于野生嚙齒動物間的一種自然疫源性疾病,。臨床上表現(xiàn)為發(fā)熱、嚴(yán)重毒血癥癥狀淋巴結(jié)腫大,、肺炎,、出血傾向等。鼠疫在世界歷史上曾有多次大流行,，在3個有記載的大流行期間導(dǎo)致了大約2億人死亡,，因此被冠上“最具毀滅性傳染病”的名頭。鼠疫耶爾森氏菌是鼠疫的病原體,，過去的研究表明其由于起源較近,，遺傳多樣性非常有限。
在這篇文章中,，研究人員解析了鼠疫耶爾森氏菌突變率的歷史演變,。對來自中國和其他地方的133個鼠疫耶爾森氏菌基因組進行了分析，鑒別出了2,326個單核苷酸多態(tài)性（SNPs）,。這些SNPs確定了從最近的共同祖先開始鼠疫耶爾森氏菌的系譜,。這些SNPs中有28個作為突變只在系譜中發(fā)生過一次，基本上隨機分布在單個基因之間,。只有7個基因有明顯過量的非同義SNP,，表明SNPs的固定（fixation）主要是通過遺傳漂移等中性演變，而非達爾文選擇進化產(chǎn)生,。然而，整個系譜固定率差異很大：不同譜系累積的SNPs數(shù)量高度變化,，系譜中包含了多分類,，其中一個導(dǎo)致了黑死病（Black Death）時間相近的4個分支,。
研究結(jié)果表明人口結(jié)構(gòu)變化可以影響傳染病病原體的進化速度,，即便在沒有自然選擇的情況下，并推測在間歇性疾病流行和爆發(fā)的過程中,，中性SNPs被快速固定,。(生物谷Bioon.com)
doi: 10.1073/pnas.1205750110
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PMID:
Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis
Yujun Cuia,b,1, Chang Yub,1, Yanfeng Yana,b,1, Dongfang Lib,1, Yanjun Lia,1, Thibaut Jombartc,1, Lucy A. Weinertd,1, Zuyun Wange, Zhaobiao Guoa, Lizhi Xub, Yujiang Zhangf, Hancheng Zhengb, Nan Qinb, Xiao Xiaoa, Mingshou Wug, Xiaoyi Wanga, Dongsheng Zhoua, Zhizhen Qie, Zongmin Dua, Honglong Wub, Xianwei Yangb, Hongzhi Caob, Hu Wange, Jing Wangh, Shusen Yaoi, Alexander Rakinj, Yingrui Lib, Daniel Falushk, Francois Ballouxd,2, Mark Achtmank,2, Yajun Songa,k,2, Jun Wangb,2, and Ruifu Yanga,b,2
The genetic diversity of Yersinia pestis, the etiologic agent of plague, is extremely limited because of its recent origin coupled with a slow clock rate. Here we identified 2,326 SNPs from 133 genomes of Y. pestis strains that were isolated in China and elsewhere. These SNPs define the genealogy of Y. pestis since its most recent common ancestor. All but 28 of these SNPs represented mutations that happened only once within the genealogy, and they were distributed essentially at random among individual genes. Only seven genes contained a significant excess of nonsynonymous SNP, suggesting that the fixation of SNPs mainly arises via neutral processes, such as genetic drift, rather than Darwinian selection. However, the rate of fixation varies dramatically over the genealogy: the number of SNPs accumulated by different lineages was highly variable and the genealogy contains multiple polytomies, one of which resulted in four branches near the time of the Black Death. We suggest that demographic changes can affect the speed of evolution in epidemic pathogens even in the absence of natural selection, and hypothesize that neutral SNPs are fixed rapidly during intermittent epidemics and outbreaks.
