Samuel Ojosnegros a,b, Niko Beerenwinkel b, Tibor Antal c, Martin A. Nowak c, Cristina Escarmís a, and
Esteban Domingo a,d,1
-Author Affiliations
aCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid. Campus de Cantoblanco, 28049 Madrid, Spain;
bDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, 4058 Basel, Switzerland;
cProgram for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138; and
d Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 08036 Barcelona, Spain
Edited by Peter Schuster, University of Vienna, Vienna, Austria, and approved November 16, 2009 (received for review September 7, 2009)
Abstract
During replication, RNA viruses rapidly generate diverse mutant progeny which differ in their ability to kill host cells. We report that the progeny of a single RNA viral genome diversified during hundreds of passages in cell culture and self-organized into two genetically distinct subpopulations that exhibited the competition-colonization dynamics previously recognized in many classical ecological systems. Viral colonizers alone were more efficient in killing cells than competitors in culture. In cells coinfected with both competitors and colonizers, viral interference resulted in reduced cell killing, and competitors replaced colonizers. Mathematical modeling of this coinfection dynamics predicted selection to be density dependent, which was confirmed experimentally. Thus, as is known for other ecological systems, biodiversity and even cell killing of virus populations can be shaped by a tradeoff between competition and colonization. Our results suggest a model for the evolution of virulence in viruses based on internal interactions within mutant spectra of viral quasispecies.
evolution quasispecies self-organization virulence
Footnotes
1To whom correspondence should be addressed. E-mail:edomingo@cbm.uam.es.
Author contributions: S.O., N.B., T.A., M.A.N., C.E., and E.D. designed research; S.O. performed research; S.O., N.B., T.A., M.A.N., and E.D. analyzed data; and S.O., N.B., and E.D. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession nos. NC002554, FJ824812, and AF274010).
This article contains supporting information online at www.pnas.org/cgi/content/full/0909787107/DCSupplemental.
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