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Here, we describe the recurrent evolution of a virulent strain of a DNA virus, which infects multiple Drosophila species. Specifically, we identified two distinct viral types that differ 100-fold in viral titer in infected individuals, with similar differences observed in multiple species. Our analysis suggests that one of the viral types recurrently evolved at least four times in the past ~30,000 years, three times in Arizona and once in another geographically distinct species. This recurrent evolution may be facilitated by an effective mutation rate which increases as each prior mutation increases viral titer and effective population size. The higher titer viral type suppresses the host-immune system and an increased virulence compared to the low viral titer type.<\/jats:p>","DOI":"10.7554\/elife.58931","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T09:00:25Z","timestamp":1603875625000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.58931","source":"Crossref","is-referenced-by-count":18,"title":["Recurrent evolution of high virulence in isolated populations of a DNA virus"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-6391","authenticated-orcid":true,"given":"Tom","family":"Hill","sequence":"first","affiliation":[{"name":"The Department of Molecular Biosciences, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8586-7137","authenticated-orcid":true,"given":"Robert L","family":"Unckless","sequence":"additional","affiliation":[{"name":"The Department of Molecular Biosciences, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.tpb.2008.04.003","article-title":"Transmission-virulence trade-offs in vector-borne diseases","volume":"74","author":"Alizon","year":"2008","journal-title":"Theoretical Population Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"Journal of Molecular Biology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1098\/rstb.1981.0005","article-title":"The population dynamics of microparasites and their invertebrate hosts","volume":"291","author":"Anderson","year":"1981","journal-title":"Philosophical Transactions of the Royal Society of London"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003537","article-title":"BEAST 2: a software platform for bayesian evolutionary analysis","volume":"10","author":"Bouckaert","year":"2014","journal-title":"PLOS Computational Biology"},{"key":"bib6","volume-title":"Scythe","author":"Buffalo","year":"2018","unstructured":"Buffalo V. 2018. 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