We thank T. F. Cooper, M. R. Goddard and D. Refardt for discussion; M. Gray, A. Hurman and G. E. M. Lamers for technical assistance; M. Ackermann, P. M. Brakefield, T. Fukami, S. Rossell and B. J. Zwaan for comments on the manuscript; T. J. M. Van Dooren for statistical advice; F. Bertels for computational analysis of Solexa data; and E. Libby for theoretical insight. This work was supported by the Marsden Fund Council from government funding administered by the Royal Society of New Zealand. H.J.E.B. is supported by a Veni Fellowship from The Netherlands Organisation for Scientific Research (NWO). J.G. was supported by a Bright Futures Scholarship from the New Zealand Foundation for Research, Science and Technology. C.K. was supported by a Feodor Lynen Fellowship from the Alexander von Humboldt Foundation, Germany. G.C.F. is supported by a Postdoctoral Fellowship from the New Zealand Foundation for Research, Science and Technology.

Author Contributions H.J.E.B. and P.B.R. conceived the research and wrote the manuscript. H.J.E.B. conducted the main selection experiment, examined the relation between cell and colony morphology, investigated reversible switching, performed genome analysis and contributed to allelic replacements. J.G. determined Cap+ cell proportions, performed transposon mutagenesis and integration-site identification, confirmed and ordered the mutations, performed allelic replacements, and contributed to fitness assays. C.K. and G.C.F. performed fitness assays. All authors commented on the manuscript