Utility of DNA viruses for studying human host history: Case study of JC virus Andrew Kitchen a, * , Michael M. Miyamoto b , Connie J. Mulligan a a Department of Anthropology, P.O. Box 103610, University of Florida, Gainesville, FL 32610-3610, USA b Department of Zoology, Box 118525, University of Florida, Gainesville, FL 32611-8525, USA Received 1 June 2007; revised 21 August 2007; accepted 6 September 2007 Available online 18 September 2007 Abstract Microbial pathogens, and viruses in particular, can serve as important complements to traditional genetic markers when investigating the population histories of their human host. The range of mutation rates for DNA viruses suggests that DNA viruses can be useful markers of both recent and ancient events in their host histories. Here, we assess the utility of a well known DNA virus, JC virus (JCV), for investigating human history and demography. Using complete coding viral genomes, we confirm the phylogeographic struc- ture of JCV in populations worldwide and provide coalescent estimates of its evolutionary rate under two alternative models of its his- tory. Using these rate estimates, we compare Bayesian skyline plots of population size changes for JCV to those of its human host as estimated with coding mitochondrial genomes of the latter. These comparisons, when combined with other evidence including a log Bayes Factor model test, show that JCV is evolving rapidly and is therefore tracking the recent history of its human host. These results support the hypothesis that post-World War II societal changes are most likely responsible for the recent demographic patterns observed among different regional JCV populations. In sum, fast evolving DNA viruses, such as JCV, can complement RNA viruses to provide novel insights about the recent history and demography of their human host. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Evolutionary rates; Historical demography; Coalescent analysis; Horizontal transmission; Co-evolution 1. Introduction Recent research has focused on the use of microbial pathogens and commensals as complements to traditional genetic markers to investigate the population histories and demographies of their hosts (Ashford, 2000; Holmes, 2004). Microbial pathogens and commensals have gener- ally faster mutation rates (l) and shorter generation times than their hosts, which thereby often produce significant population differentiation faster than that observed in any host genetic system. These attributes also offer greater resolution for the estimation of l and therefore other pop- ulation genetic parameters such as effective population size (N e ) and coalescent time. In turn, the utility of microbial pathogens and commen- sals to study host history and demography also depends on their mode of transmission (i.e., vertical, horizontal, or some mixture of both) (Ashford, 2000; Holmes, 2004). Ver- tically transmitted pathogens and commensals are passed from parents to offspring within their host populations, thereby closely tying them to their host genealogies and generation times (with the latter often measured in years to decades). Thus, such microbes are expected to show older coalescent times and slower population dynamics that reflect the more ancient historical events within their hosts. In contrast, horizontally transmitted pathogens and commensals are not so constrained as they can also be passed among unrelated individuals within their host populations by direct or indirect contact with infected non-relatives. Thus, these microbes are expected to exhibit more recent coalescent times and faster population dynam- 1055-7903/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ympev.2007.09.005 * Corresponding author. Fax: +1 352 273 8284. E-mail address: drewkit@ufl.edu (A. Kitchen). www.elsevier.com/locate/ympev Molecular Phylogenetics and Evolution 46 (2008) 673–682