来自军事医学科学院微生物流行病研究所、华大基因研究所、伦敦大学学院等研究机构的研究人员发表了题为“Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis”的研究论文，解析了鼠疫耶尔森氏菌（Yersinia pestis）突变率的历史演变。相关成果发布在《美国科学院院刊》（PNAS）上。
军事医学科学院微生物流行病研究所杨瑞馥研究员和宋亚军博士、华大基因研究所的王俊博士，以及伦敦大学学院的Francois Balloux是这篇论文的共同通讯作者。
鼠疫（plague）是鼠疫杆菌借鼠蚤传播为主的烈性传染病系广泛流行于野生啮齿动物间的一种自然疫源性疾病。临床上表现为发热、严重毒血症症状淋巴结肿大、肺炎、出血倾向等。鼠疫在世界历史上曾有多次大流行，在3个有记载的大流行期间导致了大约2亿人死亡，因此被冠上“最具毁灭性传染病”的名头。鼠疫耶尔森氏菌是鼠疫的病原体，过去的研究表明其由于起源较近，遗传多样性非常有限。
在这篇文章中，研究人员解析了鼠疫耶尔森氏菌突变率的历史演变。对来自中国和其他地方的133个鼠疫耶尔森氏菌基因组进行了分析，鉴别出了2,326个单核苷酸多态性（SNPs）。这些SNPs确定了从最近的共同祖先开始鼠疫耶尔森氏菌的系谱。这些SNPs中有28个作为突变只在系谱中发生过一次，基本上随机分布在单个基因之间。只有7个基因有明显过量的非同义SNP，表明SNPs的固定（fixation）主要是通过遗传漂移等中性演变，而非达尔文选择进化产生。然而，整个系谱固定率差异很大：不同谱系累积的SNPs数量高度变化，系谱中包含了多分类，其中一个导致了黑死病（Black Death）时间相近的4个分支。
研究结果表明人口结构变化可以影响传染病病原体的进化速度，即便在没有自然选择的情况下，并推测在间歇性疾病流行和爆发的过程中，中性SNPs被快速固定。(生物谷Bioon.com)
doi: 10.1073/pnas.1205750110
PMC:
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.
