article published yes Marjon De Vos author 3111FFAC-F248-11E8-B48F-1D18A9856A87 Alexandre Dawid author Vanda Šunderlíková author Sander Tans author ToBo department Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance. National Academy of Sciences2015 eng 26567153 00036598890005410.1073/pnas.1510282112 1124814906 - 14911 de Vos M, Dawid A, Šunderlíková V, Tans S. Breaking evolutionary constraint with a tradeoff ratchet. <i>Proceedings of the National Academy of Sciences</i>. 2015;112(48):14906-14911. doi:<a href="https://doi.org/10.1073/pnas.1510282112">10.1073/pnas.1510282112</a> M. de Vos, A. Dawid, V. Šunderlíková, S. Tans, Proceedings of the National Academy of Sciences 112 (2015) 14906–14911. M. de Vos, A. Dawid, V. Šunderlíková, and S. Tans, “Breaking evolutionary constraint with a tradeoff ratchet,” <i>Proceedings of the National Academy of Sciences</i>, vol. 112, no. 48. National Academy of Sciences, pp. 14906–14911, 2015. de Vos, Marjon, et al. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” <i>Proceedings of the National Academy of Sciences</i>, vol. 112, no. 48, National Academy of Sciences, 2015, pp. 14906–11, doi:<a href="https://doi.org/10.1073/pnas.1510282112">10.1073/pnas.1510282112</a>. Vos, Marjon de, Alexandre Dawid, Vanda Šunderlíková, and Sander Tans. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2015. <a href="https://doi.org/10.1073/pnas.1510282112">https://doi.org/10.1073/pnas.1510282112</a>. de Vos, M., Dawid, A., Šunderlíková, V., &#38; Tans, S. (2015). Breaking evolutionary constraint with a tradeoff ratchet. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1510282112">https://doi.org/10.1073/pnas.1510282112</a> de Vos M, Dawid A, Šunderlíková V, Tans S. 2015. Breaking evolutionary constraint with a tradeoff ratchet. Proceedings of the National Academy of Sciences. 112(48), 14906–14911. 15712018-12-11T11:52:47Z2025-09-23T08:03:27Z