[Source: Proceedings of the National Academy of the Sciences of the United States of America, full page: (LINK). Abstract, edited.]
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
Author Affiliations: aState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; bBeijing Genomics Institute-Shenzhen, Shenzhen 518083, China; cMedical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, United Kingdom; dUniversity College London Genetics Institute, Department of Genetics Evolution and Environment, University College London, London WC1E 6BT, United Kingdom; eQinghai Institute for Endemic Diseases Prevention and Control, Xining 811602, Qinghai Province, China; fXinjiang Center for Disease Control and Prevention, Urumiqi 830002, Xijiang province, China; gYunnan Institute for Epidemic Diseases Control and Research, Dali 671000, Yunnan Province, China; hInstitute of Health Quarantine, Chinese Academy of Inspection and Quarantine, Beijing 100025, China; iMilitary Center for Disease Control and Prevention, Beijing 100850, China; jMax von Pettenkofer Institute, Ludwig-Maximilians-University, Munich 80336, Germany; and kEnvironmental Research Institute, University College Cork, Cork, Ireland
Edited* by W. Ford Doolittle, Dalhousie University, Halifax, NS, Canada, and approved November 29, 2012 (received for review April 10, 2012)
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.
infectious disease - molecular clock – phylogenomics – NGS - molecular epidemiology
1Y.C., C.Y., Y.Y., D.L., Yanjun Li, T.J., and L.A.W. contributed equally to this work.
Author contributions: Y.C., Y.S., Jun Wang, and R.Y. designed research; Y.C., Yanjun Li, Z.G., X.X., X.W., D.Z., and Z.D. performed research; T.J., Z.W., Y.Z., N.Q., M.W., Z.Q., H. Wang, Jing Wang, S.Y., and A.R. contributed new reagents/analytic tools; Y.C., C.Y., Y.Y., D.L., T.J., L.A.W., L.X., H.Z., H. Wu, X.Y., H.C., Yingrui Li, D.F., F.B., M.A., Y.S., and R.Y. analyzed data; and Y.C., T.J., L.A.W., D.F., F.B., M.A., Y.S., and R.Y. wrote the paper.