bioRxiv preprint doi: https://doi.org/10.1101/2021.06.25.449953; this version posted July 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Metabolic resilience is encoded in genome plasticity Leandro Z. Agudelo 1, 2, † , *, Remy Tuyeras1, 2, † , *, Claudia Llinares4, Alvaro Morcuende4, Yongjin Park1,2, Na Sun1, 2, Suvi Linna-Kuosmanen1, 2, Naeimeh Atabaki-Pasdar1, 6, Li-Lun Ho1, 2, Kyriakitsa Galani1, 2, Paul W. Franks6, 7, Burak Kutlu5, Kevin Grove5, Teresa Femenia3, 4, *, and Manolis Kellis1, 2, * 1 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge MA, USA 2 Broad Institute of MIT and Harvard, Cambridge MA, USA 3 Department of Neuroscience, Karolinska Institutet, Biomedicum, Stockholm, Sweden 4 Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain 5 Novo Nordisk Research Center Seattle, Washington, USA 6 Department of Clinical Sciences, Lund University, Lund, Sweden 7 Department of Nutrition, Harvard School of Public Health, Boston MA, USA † These authors contributed equally to this work * Corresponding authors:
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[email protected] Abstract Metabolism plays a central role in evolution, as resource conservation is a selective pressure for fitness and survival. Resource-driven adaptations offer a good model to study evolutionary innovation more broadly. It remains unknown how resource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions. Here we show that tuning of genome architecture and heterotypic transcriptional condensates mediate resilience to nutrient limitation.