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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>Inheritance is central to life, but its first chemical basis may have preceded the complex molecules that store genetic information in modern organisms. Molecules in autocatalytic chemical networks facilitate the formation of more instances of the same molecules. They have long been proposed as simpler candidates for primitive heredity, yet it has remained unclear how such systems could show stable, selectable variation rather than mere short-term adjustment to changing conditions. Here we show that two mutually interacting autocatalytic networks can form alternative stable chemical states, maintained by weak cross-catalysis and switched by environmental change when enclosed in reproducing compartments. Rare compartments dominated by the previously unfavored autocatalyst arise through stochastic partitioning at division and are then amplified by selection in a changed environment, producing an analog of genetic adaptation before template-based replication. The results suggest that primitive inheritance could have been attractor-based, collective, and chemical, rather than sequence-based from the outset. They also identify a concrete dynamical signature to seek in experimental systems chemistry: compartmentalized autocatalytic networks that retain memory of past states while remaining able to switch under selection. Such behavior would extend evolutionary reasoning to a pregenetic stage of life\u2019s origin and clarify how protocell-level evolution could begin before modern genes existed.<\/jats:p>","DOI":"10.1073\/pnas.2621400123","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:05Z","timestamp":1790017925000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Bistability of compartmentalized autocatalytic systems at the dawn of hereditary variation"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3541-0195","authenticated-orcid":false,"given":"Alexa","family":"Iv\u00e1n","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01crqqh49","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for the Conceptual Foundations of Science, Parmenides Foundation","place":["P\u00f6cking, Germany"]},{"id":[{"id":"https:\/\/ror.org\/04bhfmv97","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Evolution, Hungarian Research Network Centre for Ecological Research","place":["Budapest, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01jsq2704","id-type":"ROR","asserted-by":"publisher"}],"name":"Doctoral School of Biology, E\u00f6tv\u00f6s Lor\u00e1nd University","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-4652","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Szil\u00e1gyi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01crqqh49","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for the Conceptual Foundations of Science, Parmenides Foundation","place":["P\u00f6cking, Germany"]},{"id":[{"id":"https:\/\/ror.org\/04bhfmv97","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Evolution, Hungarian Research Network Centre for Ecological Research","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-2997","authenticated-orcid":false,"given":"E\u00f6rs","family":"Szathm\u00e1ry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01crqqh49","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for the Conceptual Foundations of Science, Parmenides Foundation","place":["P\u00f6cking, Germany"]},{"id":[{"id":"https:\/\/ror.org\/04bhfmv97","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Evolution, Hungarian Research Network Centre for Ecological Research","place":["Budapest, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01jsq2704","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Plant Systematics, Ecology and Theoretical Biology, E\u00f6tv\u00f6s Lor\u00e1nd University","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198507260.001.0001"},{"key":"e_1_3_4_2_2","volume-title":"The Major Transitions in Evolution","author":"Maynard Smith J.","year":"1995","unstructured":"J. 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