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.
↵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.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
Data deposition: Raw genome data have been deposited in the National Center for Biotechnology Information/Short Read archive database, www.ncbi.nlm.nih.gov/sra (accession no SRA010790; individual genome assemblies have been deposited under accession nos. ADOV00000000 47685–ADTI00000000 47685). The accession numbers for each strain are listed in Dataset S1.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1205750110/-/DCSupplemental.
