{"bundle_type":"pith_open_graph_bundle","bundle_version":"1.0","pith_number":"pith:2013:HPIE5VRBVFQ62EY3LR2GLGWW42","short_pith_number":"pith:HPIE5VRB","canonical_record":{"source":{"id":"1309.1152","kind":"arxiv","version":2},"metadata":{"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.PE","submitted_at":"2013-09-04T19:55:33Z","cross_cats_sorted":[],"title_canon_sha256":"2e2b8138ef15c58789a569b418d7da8237fc94a86cb008224f1fe3823e03b383","abstract_canon_sha256":"f608afb33995120f22ca3fbc31c80fbab7dd319598b437fdf17cc5adff9bc6e1"},"schema_version":"1.0"},"canonical_sha256":"3bd04ed621a961ed131b5c74659ad6e6be44c7c7fe4e2d5f419446534277d329","source":{"kind":"arxiv","id":"1309.1152","version":2},"source_aliases":[{"alias_kind":"arxiv","alias_value":"1309.1152","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"arxiv_version","alias_value":"1309.1152v2","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.1309.1152","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"pith_short_12","alias_value":"HPIE5VRBVFQ6","created_at":"2026-05-18T12:27:46Z"},{"alias_kind":"pith_short_16","alias_value":"HPIE5VRBVFQ62EY3","created_at":"2026-05-18T12:27:46Z"},{"alias_kind":"pith_short_8","alias_value":"HPIE5VRB","created_at":"2026-05-18T12:27:46Z"}],"events":[{"event_type":"record_created","subject_pith_number":"pith:2013:HPIE5VRBVFQ62EY3LR2GLGWW42","target":"record","payload":{"canonical_record":{"source":{"id":"1309.1152","kind":"arxiv","version":2},"metadata":{"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.PE","submitted_at":"2013-09-04T19:55:33Z","cross_cats_sorted":[],"title_canon_sha256":"2e2b8138ef15c58789a569b418d7da8237fc94a86cb008224f1fe3823e03b383","abstract_canon_sha256":"f608afb33995120f22ca3fbc31c80fbab7dd319598b437fdf17cc5adff9bc6e1"},"schema_version":"1.0"},"canonical_sha256":"3bd04ed621a961ed131b5c74659ad6e6be44c7c7fe4e2d5f419446534277d329","receipt":{"kind":"pith_receipt","key_id":"pith-v1-2026-05","algorithm":"ed25519","signed_at":"2026-05-18T02:25:26.720618Z","signature_b64":"4SmlL5Brg9QxJu3z0AvtbKfhx8vQThYZrWrP/J78uT/D9rcjFusa+CfS8fw9mdnaNkkBI265R1IvXb34pAv3DQ==","signed_message":"canonical_sha256_bytes","builder_version":"pith-number-builder-2026-05-17-v1","receipt_version":"0.3","canonical_sha256":"3bd04ed621a961ed131b5c74659ad6e6be44c7c7fe4e2d5f419446534277d329","last_reissued_at":"2026-05-18T02:25:26.720204Z","signature_status":"signed_v1","first_computed_at":"2026-05-18T02:25:26.720204Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"source_kind":"arxiv","source_id":"1309.1152","source_version":2,"attestation_state":"computed"},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-05-18T02:25:26Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"ll1blSPVU09Nc385NrbC/iUT4jI5h1hOz8POjFn83ljI2ke2RTogBJMjCV2rIw4ytTVMg3oQJcqCzoZ10fZoCg==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-05-29T19:20:30.619278Z"},"content_sha256":"ad8b416d615e7d0dadea58577e2314ae150ba24ea42d0ea6c6d4c54f2a9d417b","schema_version":"1.0","event_id":"sha256:ad8b416d615e7d0dadea58577e2314ae150ba24ea42d0ea6c6d4c54f2a9d417b"},{"event_type":"graph_snapshot","subject_pith_number":"pith:2013:HPIE5VRBVFQ62EY3LR2GLGWW42","target":"graph","payload":{"graph_snapshot":{"paper":{"title":"The inevitability of unconditionally deleterious substitutions during adaptation","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","headline":"","cross_cats":[],"primary_cat":"q-bio.PE","authors_text":"Charles L. Epstein, David M. McCandlish, Joshua B. Plotkin","submitted_at":"2013-09-04T19:55:33Z","abstract_excerpt":"Studies on the genetics of adaptation typically neglect the possibility that a deleterious mutation might fix. Nonetheless, here we show that, in many regimes, the first substitution is most often deleterious, even when fitness is expected to increase in the long term. In particular, we prove that this phenomenon occurs under weak mutation for any house-of-cards model with an equilibrium distribution. We find that the same qualitative results hold under Fisher's geometric model. We also provide a simple intuition for the surprising prevalence of unconditionally deleterious substitutions during"},"claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"1309.1152","kind":"arxiv","version":2},"verdict":{"id":null,"model_set":{},"created_at":null,"strongest_claim":"","one_line_summary":"","pipeline_version":null,"weakest_assumption":"","pith_extraction_headline":""},"references":{"count":0,"sample":[],"resolved_work":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","internal_anchors":0},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"},"verdict_id":null},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-05-18T02:25:26Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"Yzx3viKqIV3w4PUnT/XoPmGstXpVk2tQj/b9jJjeQewy7rsf22PL1mbFjyajO7Mgj/jooL1sc8kyDqnPCDCsBQ==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-05-29T19:20:30.619942Z"},"content_sha256":"cfe7765da5f9953b5bfab76e9c1115c6dead143db4c382aaacda675454f0dc39","schema_version":"1.0","event_id":"sha256:cfe7765da5f9953b5bfab76e9c1115c6dead143db4c382aaacda675454f0dc39"}],"timestamp_proofs":[],"mirror_hints":[{"mirror_type":"https","name":"Pith Resolver","base_url":"https://pith.science","bundle_url":"https://pith.science/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/bundle.json","state_url":"https://pith.science/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/state.json","well_known_bundle_url":"https://pith.science/.well-known/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/bundle.json","status":"primary"}],"public_keys":[{"key_id":"pith-v1-2026-05","algorithm":"ed25519","format":"raw","public_key_b64":"stVStoiQhXFxp4s2pdzPNoqVNBMojDU/fJ2db5S3CbM=","public_key_hex":"b2d552b68890857171a78b36a5dccf368a953413288c353f7c9d9d6f94b709b3","fingerprint_sha256_b32_first128bits":"RVFV5Z2OI2J3ZUO7ERDEBCYNKS","fingerprint_sha256_hex":"8d4b5ee74e4693bcd1df2446408b0d54","rotates_at":null,"url":"https://pith.science/pith-signing-key.json","notes":"Pith uses this Ed25519 key to sign canonical record SHA-256 digests. Verify with: ed25519_verify(public_key, message=canonical_sha256_bytes, signature=base64decode(signature_b64))."}],"merge_version":"pith-open-graph-merge-v1","built_at":"2026-05-29T19:20:30Z","links":{"resolver":"https://pith.science/pith/HPIE5VRBVFQ62EY3LR2GLGWW42","bundle":"https://pith.science/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/bundle.json","state":"https://pith.science/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/state.json","well_known_bundle":"https://pith.science/.well-known/pith/HPIE5VRBVFQ62EY3LR2GLGWW42/bundle.json"},"state":{"state_type":"pith_open_graph_state","state_version":"1.0","pith_number":"pith:2013:HPIE5VRBVFQ62EY3LR2GLGWW42","merge_version":"pith-open-graph-merge-v1","event_count":2,"valid_event_count":2,"invalid_event_count":0,"equivocation_count":0,"current":{"canonical_record":{"metadata":{"abstract_canon_sha256":"f608afb33995120f22ca3fbc31c80fbab7dd319598b437fdf17cc5adff9bc6e1","cross_cats_sorted":[],"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.PE","submitted_at":"2013-09-04T19:55:33Z","title_canon_sha256":"2e2b8138ef15c58789a569b418d7da8237fc94a86cb008224f1fe3823e03b383"},"schema_version":"1.0","source":{"id":"1309.1152","kind":"arxiv","version":2}},"source_aliases":[{"alias_kind":"arxiv","alias_value":"1309.1152","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"arxiv_version","alias_value":"1309.1152v2","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.1309.1152","created_at":"2026-05-18T02:25:26Z"},{"alias_kind":"pith_short_12","alias_value":"HPIE5VRBVFQ6","created_at":"2026-05-18T12:27:46Z"},{"alias_kind":"pith_short_16","alias_value":"HPIE5VRBVFQ62EY3","created_at":"2026-05-18T12:27:46Z"},{"alias_kind":"pith_short_8","alias_value":"HPIE5VRB","created_at":"2026-05-18T12:27:46Z"}],"graph_snapshots":[{"event_id":"sha256:cfe7765da5f9953b5bfab76e9c1115c6dead143db4c382aaacda675454f0dc39","target":"graph","created_at":"2026-05-18T02:25:26Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"graph_snapshot":{"author_claims":{"count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","strong_count":0},"builder_version":"pith-number-builder-2026-05-17-v1","claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"paper":{"abstract_excerpt":"Studies on the genetics of adaptation typically neglect the possibility that a deleterious mutation might fix. Nonetheless, here we show that, in many regimes, the first substitution is most often deleterious, even when fitness is expected to increase in the long term. In particular, we prove that this phenomenon occurs under weak mutation for any house-of-cards model with an equilibrium distribution. We find that the same qualitative results hold under Fisher's geometric model. We also provide a simple intuition for the surprising prevalence of unconditionally deleterious substitutions during","authors_text":"Charles L. Epstein, David M. McCandlish, Joshua B. Plotkin","cross_cats":[],"headline":"","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.PE","submitted_at":"2013-09-04T19:55:33Z","title":"The inevitability of unconditionally deleterious substitutions during adaptation"},"references":{"count":0,"internal_anchors":0,"resolved_work":0,"sample":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"1309.1152","kind":"arxiv","version":2},"verdict":{"created_at":null,"id":null,"model_set":{},"one_line_summary":"","pipeline_version":null,"pith_extraction_headline":"","strongest_claim":"","weakest_assumption":""}},"verdict_id":null}}],"author_attestations":[],"timestamp_anchors":[],"storage_attestations":[],"citation_signatures":[],"replication_records":[],"corrections":[],"mirror_hints":[],"record_created":{"event_id":"sha256:ad8b416d615e7d0dadea58577e2314ae150ba24ea42d0ea6c6d4c54f2a9d417b","target":"record","created_at":"2026-05-18T02:25:26Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"attestation_state":"computed","canonical_record":{"metadata":{"abstract_canon_sha256":"f608afb33995120f22ca3fbc31c80fbab7dd319598b437fdf17cc5adff9bc6e1","cross_cats_sorted":[],"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.PE","submitted_at":"2013-09-04T19:55:33Z","title_canon_sha256":"2e2b8138ef15c58789a569b418d7da8237fc94a86cb008224f1fe3823e03b383"},"schema_version":"1.0","source":{"id":"1309.1152","kind":"arxiv","version":2}},"canonical_sha256":"3bd04ed621a961ed131b5c74659ad6e6be44c7c7fe4e2d5f419446534277d329","receipt":{"algorithm":"ed25519","builder_version":"pith-number-builder-2026-05-17-v1","canonical_sha256":"3bd04ed621a961ed131b5c74659ad6e6be44c7c7fe4e2d5f419446534277d329","first_computed_at":"2026-05-18T02:25:26.720204Z","key_id":"pith-v1-2026-05","kind":"pith_receipt","last_reissued_at":"2026-05-18T02:25:26.720204Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","receipt_version":"0.3","signature_b64":"4SmlL5Brg9QxJu3z0AvtbKfhx8vQThYZrWrP/J78uT/D9rcjFusa+CfS8fw9mdnaNkkBI265R1IvXb34pAv3DQ==","signature_status":"signed_v1","signed_at":"2026-05-18T02:25:26.720618Z","signed_message":"canonical_sha256_bytes"},"source_id":"1309.1152","source_kind":"arxiv","source_version":2}}},"equivocations":[],"invalid_events":[],"applied_event_ids":["sha256:ad8b416d615e7d0dadea58577e2314ae150ba24ea42d0ea6c6d4c54f2a9d417b","sha256:cfe7765da5f9953b5bfab76e9c1115c6dead143db4c382aaacda675454f0dc39"],"state_sha256":"81bc4956b486dba3d9f2bfe92f004b206666e4edd10f952bb56254a3e376cd3b"},"bundle_signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"yxWu9WB2pqsfDmpLni+V1N7ZkNZtAc8flNMp/anuxVZ9w3RYSD7tPrsGT74/ANSr+xd4xqZQZdACiYFY2+OJDA==","signed_message":"bundle_sha256_bytes","signed_at":"2026-05-29T19:20:30.623667Z","bundle_sha256":"1a8676cacd9960f417f88536c904f6dc6273cc00549bef89684027ad1198c52e"}}