{"doi":"10.1101/2025.10.06.680734","title":"Adaptive Disruption of Carotenoid Metabolism in Cavefish via Loss of Beta-carotene oxygenase 2a (Bco2a)","abstract":"Summary Vitamin A is an essential micronutrient that supports vision, immunity, and development, yet excess vitamin A can be toxic 1,2 . Most vertebrates maintain tightly regulated vitamin A levels by cleaving dietary carotenoids into retinoids via specialized enzymes, including the mitochondrial carotenoid oxygenase Bco2 3,4 . To what extent genetic changes in carotenoid-metabolism enzymes like Bco2 drive natural variation in vitamin A homeostasis remains unclear. Here we show that multiple cave-adapted populations of the Mexican tetra ( Astyanax mexicanus ) have evolved loss-of-function mutations in bco2a , leading to impaired carotenoid cleavage and dramatic carotenoid and vitamin A accumulation. These mutations yield enzymatically inactive Bco2a proteins, are under selection in cavefish, and may provide a physiological advantage under inconsistent carotenoid supply. Contrary to expectations from mammalian models where Bco2 loss induces oxidative damage 5,6 , cavefish appear to tolerate and even benefit from carotenoid accumulation, potentially through enhanced antioxidant capacity and modified mitochondrial metabolism. Our findings reveal that the vitamin A regulatory system is evolutionarily flexible, and that the adaptive loss of Bco2a function may enable survival in nutrient-variable, low-oxygen cave environments. This work provides a framework for understanding how animals balance essential nutrient thresholds in extreme environments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559238,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":417587,"name":"Sepalika Bandara","orcid":"0000-0003-1029-1457","position":1,"is_corresponding":false},{"id":685990,"name":"Francisca Leal","orcid":null,"position":2,"is_corresponding":false},{"id":315246,"name":"Johannes von Lintig","orcid":"0000-0002-2079-2143","position":3,"is_corresponding":false},{"id":544330,"name":"Misty R. Riddle","orcid":"0000-0003-4024-2752","position":4,"is_corresponding":false},{"id":1461048,"name":"D. Guerra","orcid":null,"position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41279145","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}