{"schema":"pubphys.bundle/1","record":{"author":{"account_ref":null,"orcid":null},"builds_on":[],"content_schema":"pubphys.content.revision/1","content_sha256":"9fcb2a5fae2bbeaad4993d545415febe756bfab47d283a5671b44c630cf84ed6","created":"2026-10-03T07:17:57Z","files":[],"origin":{"assisted_by":[],"kind":"seed"},"parents":["04a07534a4674012205049a37eca4242997448e6585b6a3c8772245c6d4fc256","5475cf5dc5b1a72283d26dc95dc6e00d7ea4e00096a7c6492e409a1816eeb011"],"salt":"af937550b4386814ac13079007b56da4b7f78288b7ef7eff75b46dec30973e7f","schema":"pubphys.record/2","site":"pubphys.com","target":null,"type":"revision"},"content":{"answer_type":"mechanism","assisted_by":[],"external_id":"bio.fitness-landscapes.global-epistasis","kind":"well-posed","literature_status":"partially-resolved","n":"1","parents":[{"note":"","parent_revision":"04a07534a4674012205049a37eca4242997448e6585b6a3c8772245c6d4fc256","relation":"special_case"}],"plain":"In many experiments a beneficial mutation helps less in a fitter genome, as if all mutations interact through one shared fitness value. Whether this pattern emerges generically from many hidden molecular interactions, and when, is not settled.","posed_since":"","precise":"Global epistasis: the effect s of a mutation depends approximately linearly on background fitness F, $s \\sim a - b F \\text{ with } b > 0$, across many yeast and E. coli data sets. Determine the conditions on a microscopic genotype-to-fitness map (random additive plus pairwise interactions, nonlinear phenotype-to-fitness maps) under which this linear dependence holds for most mutations, and predict b from measurable quantities.","problem_ref":null,"references":"","settled_by":"A theory predicting the distribution of slopes b from independently measured interaction statistics, confirmed on combinatorial mutant data.","status_note":"A 2021 model (Reddy and Desai) showed that many idiosyncratic interactions generically produce global epistasis; conditions and slope values remain open.","title":"Why diminishing-returns epistasis is so 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