title: Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis.
abstract: 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.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity,  Beijing Institute of Microbiology and Epidemiology, Beijing 100071,  China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Cui
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Dongfang
authors.initials: D
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jombart
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Weinert
authors.forename: Zuyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhaobiao
authors.initials: Z
authors.lastname: Guo
authors.forename: Lizhi
authors.initials: L
authors.lastname: Xu
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Nan
authors.initials: N
authors.lastname: Qin
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Mingshou
authors.initials: M
authors.lastname: Wu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Qi
authors.forename: Zongmin
authors.initials: Z
authors.lastname: Du
authors.forename: Honglong
authors.initials: H
authors.lastname: Wu
authors.forename: Xianwei
authors.initials: X
authors.lastname: Yang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shusen
authors.initials: S
authors.lastname: Yao
authors.forename: Alexander
authors.initials: A
authors.lastname: Rakin
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Falush
authors.forename: Francois
authors.initials: F
authors.lastname: Balloux
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.forename: Yajun
authors.initials: Y
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D002681:China; D019143:Evolution, Molecular; D040961:Genetic Drift; D014644:Genetic Variation; D005828:Genetics, Population; D016013:Likelihood Functions; D008957:Models, Genetic; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D059645:Mutation Rate; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D015010:Yersinia pestis / Q000235:genetics*