Monjane, A.L.Martin, P.Lakay, F.Muhire, B.Pande, P.Varsani, A.Harkins, G.Shepherd, D.N.Rybicki, E.P.2014-08-142014-08-142014Monjane, A.L., Martin, P., Lakay, F., Muhire, B., Pande, P., Varsani, A., Harkins, G., Shepherd, D.N., Rybicki, E.P. (2014) Extensive recombination–induced disruption of genetic interactions is highly deleterious but can be partially reversed by small numbers of secondary-recombination events. Journal of Virology, 88(14), pp. 7843–7851.http://hdl.handle.net/10092/9498Although homologous recombination can potentially provide viruses with vastly more evolutionary options than are available through mutation alone, there are considerable limits on the adaptive potential of this important evolutionary process. Primary among these is the disruption of favorable coevolved genetic interactions that can occur following the transfer of foreign genetic material into a genome. Although the fitness costs of such disruptions can be severe, in some cases they can be rapidly recouped by either compensatory mutations or secondary recombination events. Here, we used a maize streak virus (MSV) experimental model to explore both the extremes of recombination-induced genetic disruption and the capacity of secondary recombination to adaptively reverse almost lethal recombination events. Starting with two naturally occurring parental viruses, we synthesized two of the most extreme conceivable MSV chimeras, each effectively carrying 182 recombination breakpoints and containing thorough reciprocal mixtures of parental polymorphisms. Although both chimeras were severely defective and apparently noninfectious, neither had individual movement-, encapsidation-, or replication-associated genome regions that were on their own “lethally recombinant.” Surprisingly, mixed inoculations of the chimeras yielded symptomatic infections with viruses with secondary recombination events. These recombinants had only 2 to 6 breakpoints, had predominantly inherited the least defective of the chimeric parental genome fragments, and were obviously far more fit than their synthetic parents. It is clearly evident, therefore, that even when recombinationally disrupted virus genomes have extremely low fitness and there are no easily accessible routes to full recovery, small numbers of secondary recombination events can still yield tremendous fitness gains.enJournal ArticleField of Research::06 - Biological Sciences::0604 - GeneticsFields of Research::31 - Biological sciences::3107 - Microbiology::310706 - Virologyhttps://doi.org/10.1128/JVI.00709-14