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Here, we systematically tested whether harmful loss of metabolic genes, followed by compensatory evolution, generates preadaptations to alternative nutrients in Escherichia coli. Our analysis revealed a striking outcome beyond simple growth restoration, where repair of a genetic defect yielded growth exceeding the unperturbed wild type on carbon sources not encountered during evolution. Such latent growth gains occurred across multiple deletion backgrounds and carbon sources, with growth rate increases up to 46% relative to the wild type. In some cases, the corresponding ancestral deletion strain failed to grow on these carbon sources, indicating functional innovations relative to the deletion ancestor. Genetic reconstruction and transcriptomic profiling implicate regulatory reprogramming, particularly in carbon catabolite repression and nutrient uptake, as mechanisms underlying latent growth gains. In conclusion, evolutionary recovery from gene loss can rapidly produce preadaptations to future environments in the absence of direct selection.<\/jats:p>","DOI":"10.1093\/molbev\/msag143","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:44:30Z","timestamp":1781178270000},"source":"Crossref","is-referenced-by-count":0,"title":["Gene loss and compensatory evolution as a source of metabolic preadaptations"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5830-8249","authenticated-orcid":false,"given":"Dorottya","family":"Kalapis","sequence":"first","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, National Laboratory of Biotechnology, HUN-REN Biological Research Centre , Temesv\u00e1ri Krt. 62, Szeged 6726 ,","place":["Hungary"]},{"name":"HCEMM-BRC Metabolic Systems Biology Group , Temesv\u00e1ri Krt. 62, Szeged 6726 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