Kerr, Peter J.Ghedin, ElodieDePasse, Jay V.Fitch, AdamCattadori, Isabella M.Hudson, Peter J.Tscharke, David C.Read, Andrew F.Holmes, Edward C.2015-11-272015-11-271553-7374http://hdl.handle.net/1885/16863The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.This work was funded in part by grant R01 AI093804-01A1 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (http://www.niaid.nih.gov/Pages/default.aspx). We thank members of the Research and Policy in Infectious Disease Dynamics Program of the Science and Technology Directorate, Department of Homeland Security (http://www.dhs.gov/index.shtm) and the Fogarty International Center, National Institutes of Health (http://www.fic.nih.gov/Pages/Default.aspx)for support. We also thank the Huck Institutes of Life Sciences, The Pennsylvania State University (http://www.huck.psu.edu/), for seed funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.© Kerr et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.animalsaustraliabase sequencebiological evolutiondna, viraleuropemolecular sequence datamutation ratemyxoma virusmyxomatosis, infectiousphylogenyrabbitssequence analysis, dnaevolution, moleculargenome, viral2012-10-0410.1371/journal.ppat.10029502015-12-10