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Experimental evolution strategies to modulate bacteriophage life-history traits Manuela Reuter, Michael Sieber1, Octavio Reyes-Matte1, Christina Vasileiou1, Jordan Romeyer-Dherbey2, Christopher Böhmker1, Javier Lopez-Garrido1, Frederic Bertels1 1Max Planck Institute for Evolutionary Biology, Plön, Germany 2University of Cambridge, Cambridge, United Kingdom Bacteriophage’s life-history traits such as the rate of attachment to the host, the duration of the infection cycle, the number of progeny produced per infected cell, and the ability to persist in the environment determine whether a phage infection will be productive. Here, we show that subtle differences in transfer times during serial passaging can select for drastically different phage life-history trait phenotypes. Long transfer times led to highly persistent phages with a high adsorption rate, while short transfers selected for slow adsorbing mutants with low persistence. Simulations of both transfer regimes predicted that slow adsorption alone could explain the evolution of the short-transfer mutant on the observed time scale, while selection on persistence and adsorption was required to predict the emergence of long transfer mutants. Changes in adsorption and persistence were caused by a single-point mutation in the major capsid protein. The proximity of these very different phenotypes in genotypic space may be the result of frequent adaptation to different environments that select for life history traits associated with a specific plaque phenotype. Our results demonstrate that evolution experiments can be used to efficiently switch between these phenotypes, which may also be important for improving the efficacy of therapeutic phages.