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. 2007 May 8;104(19):7993-8.
doi: 10.1073/pnas.0700741104. Epub 2007 Apr 30.

A high-resolution genetic signature of demographic and spatial expansion in epizootic rabies virus

Affiliations

A high-resolution genetic signature of demographic and spatial expansion in epizootic rabies virus

Roman Biek et al. Proc Natl Acad Sci U S A. .

Abstract

Emerging pathogens potentially undergo rapid evolution while expanding in population size and geographic range during the course of invasion, yet it is generally difficult to demonstrate how these processes interact. Our analysis of a 30-yr data set covering a large-scale rabies virus outbreak among North American raccoons reveals the long lasting effect of the initial infection wave in determining how viral populations are genetically structured in space. We further find that coalescent-based estimates derived from the genetic data yielded an amazingly accurate reconstruction of the known spatial and demographic dynamics of the virus over time. Our study demonstrates the combined evolutionary and population dynamic processes characterizing the spread of pathogen after its introduction into a fully susceptible host population. Furthermore, the results provide important insights regarding the spatial scale of rabies persistence and validate the use of coalescent approaches for uncovering even relatively complex population histories. Such approaches will be of increasing relevance for understanding the epidemiology of emerging zoonotic diseases in a landscape context.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Phylogenetic relationships among virus samples collected during a RRV epizootic in eastern North America. (A) Maximum clade credibility (MCC) tree from Bayesian coalescent analysis (32). Color-coding of branches distinguishes seven lineages (see Materials and Methods). Clade credibility values >50% are shown up to the lineage level only; nodes within lineages that received >70% posterior support are indicated by asterisks. (B) Portion of MCC tree that corresponds to initial infection wave projected onto the landscape. Tree tips represent centroids of counties that were sampled during the initial wave (i.e., collected within 37 months of the first reported case of RRV in that county). Latitude and longitude of nodes (including root, shown as black star) were estimated by using phylogenetic generalized least squares (37). White star marks Pendleton County, WV, where the epizootic's first case was reported in 1977. (C) Full MCC tree projected onto landscape, including samples collected 4–14 (squares) and 15–25 yr (triangles) after the first county case. Maps were produced with the help of online map creator (available at www.aquarius.geomar.de/omc/).
Fig. 2.
Fig. 2.
Number of RRV infections, 1977–2005, estimated from genetic and case data. Median effective number of RRV infections (thick black line) was estimated by using a Bayesian skyline plot and represents the product of effective population size (Ne) and generation time (τ) in years. Thin black lines represent 95% highest posterior density (HPD) intervals. Estimated time associated with the most recent common ancestor is indicated by red dashed line; HPD interval is shown as pink shaded area. Light blue line represents the 15-months moving average of the monthly area (in km2) newly affected by RRV between 1977 and 1999 as an index of the number of rabid raccoons through time. Exponen., exponential.
Fig. 3.
Fig. 3.
Annual rate of RRV spread along the U.S. mid- Atlantic relative to elevation and major rivers, 1977–1999. Annual contours of spread were computed based on the date of the first case of RRV reported in a county by using a kriging routine available in ArcGIS Geostatistical Analyst (42). Colors of contours distinguish periods of fast and slow viral population growth (see Fig. 2) that were identified from coalescent demographic analysis. Thicker lines indicate the respective endpoints of demographic periods.

References

    1. Daszak P, Cunningham AA, Hyatt AD. Science. 2000;287:443–449. - PubMed
    1. Swinton J, Harwood J, Grenfell BT, Gilligan CA. J Anim Ecol. 1998;67:54–68.
    1. Fischer JR, Stallknecht DE, Luttrell P, Dhondt AA, Converse KA. Emerg Infect Dis. 1997;3:69–72. - PMC - PubMed
    1. Real LA, Henderson JC, Biek R, Snaman J, Jack TL, Childs JE, Stahl E, Waller LA, Tinline R, Nadin-Davis S. Proc Natl Acad Sci USA. 2005;102:12107–12111. - PMC - PubMed
    1. Holmes EC. Mol Ecol. 2004;13:745–756. - PubMed

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