A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms
Summary: Independent lineages showing similar phenotypic traits can use different genetic paths to achieve the same phenotypic outcome. Instances of such convergence at the genotypic level, however, remain underexplored. In this study, we generated and used a homozygous knock-in mouse model to chara...
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225011356 |
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| author | Amruta Swaminathan Alexander Kenzior Andrew Price Hua Li Colin McCoin Aurélie Hintermann Kyle Weaver NatiCia Morris Alex C. Keene Nicolas Rohner |
| author_facet | Amruta Swaminathan Alexander Kenzior Andrew Price Hua Li Colin McCoin Aurélie Hintermann Kyle Weaver NatiCia Morris Alex C. Keene Nicolas Rohner |
| author_sort | Amruta Swaminathan |
| collection | DOAJ |
| description | Summary: Independent lineages showing similar phenotypic traits can use different genetic paths to achieve the same phenotypic outcome. Instances of such convergence at the genotypic level, however, remain underexplored. In this study, we generated and used a homozygous knock-in mouse model to characterize a previously identified mutation, CRY1 R263Q, that has repeatedly evolved in a highly conserved protein domain across lineages adapted to caves and subterranean environments. Indirect calorimetry experiments revealed that the mutation alters circadian patterns of energy expenditure, locomotor activity, and feeding behaviors in the dark phase, but no further metabolic phenotypes. We also found that the mutation causes the aberrant expression of canonical circadian and metabolic genes in the liver, consistent with circadian clock and metabolic dysregulation reported in subterranean dwellers, which may be adaptive in such environments. Our work highlights the capacity for selection to drive repeated phenotypic evolution through repetitions of the same underlying genetic change. |
| format | Article |
| id | doaj-art-1f3ca6dcfce94ddf9ec737abf6181a52 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-1f3ca6dcfce94ddf9ec737abf6181a522025-08-20T02:35:00ZengElsevieriScience2589-00422025-07-0128711287410.1016/j.isci.2025.112874A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythmsAmruta Swaminathan0Alexander Kenzior1Andrew Price2Hua Li3Colin McCoin4Aurélie Hintermann5Kyle Weaver6NatiCia Morris7Alex C. Keene8Nicolas Rohner9Stowers Institute for Medical Research, Kansas City, MO 64110, USAStowers Institute for Medical Research, Kansas City, MO 64110, USAStowers Institute for Medical Research, Kansas City, MO 64110, USAStowers Institute for Medical Research, Kansas City, MO 64110, USADepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USAStowers Institute for Medical Research, Kansas City, MO 64110, USAStowers Institute for Medical Research, Kansas City, MO 64110, USAStowers Institute for Medical Research, Kansas City, MO 64110, USADepartment of Biology, Texas A&M University, College Station, TX 77840, USAStowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Corresponding authorSummary: Independent lineages showing similar phenotypic traits can use different genetic paths to achieve the same phenotypic outcome. Instances of such convergence at the genotypic level, however, remain underexplored. In this study, we generated and used a homozygous knock-in mouse model to characterize a previously identified mutation, CRY1 R263Q, that has repeatedly evolved in a highly conserved protein domain across lineages adapted to caves and subterranean environments. Indirect calorimetry experiments revealed that the mutation alters circadian patterns of energy expenditure, locomotor activity, and feeding behaviors in the dark phase, but no further metabolic phenotypes. We also found that the mutation causes the aberrant expression of canonical circadian and metabolic genes in the liver, consistent with circadian clock and metabolic dysregulation reported in subterranean dwellers, which may be adaptive in such environments. Our work highlights the capacity for selection to drive repeated phenotypic evolution through repetitions of the same underlying genetic change.http://www.sciencedirect.com/science/article/pii/S2589004225011356ChronobiologyEvolutionary biologyMolecular biologyZoology |
| spellingShingle | Amruta Swaminathan Alexander Kenzior Andrew Price Hua Li Colin McCoin Aurélie Hintermann Kyle Weaver NatiCia Morris Alex C. Keene Nicolas Rohner A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms iScience Chronobiology Evolutionary biology Molecular biology Zoology |
| title | A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms |
| title_full | A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms |
| title_fullStr | A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms |
| title_full_unstemmed | A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms |
| title_short | A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms |
| title_sort | repeatedly evolved mutation in cryptochrome 1 of subterranean animals alters behavioral and molecular circadian rhythms |
| topic | Chronobiology Evolutionary biology Molecular biology Zoology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225011356 |
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