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Snakes, with their remarkable physiological, metabolic, and morphological adaptations, serve as powerful models for investigating these processes. Burmese pythons (Python bivittatus) have been used as a model for studying the plasticity of extreme physiological systems. The low contiguity of the P. bivittatus genome and rising challenges in obtaining Burmese pythons for study prompted us to sequence, assemble, and annotate the genome of the closely related ball python (Python regius). Using a hybrid sequencing approach, we generated a 1.45-Gb genome assembly with a scaffold N50 greater than 61\u2005Mb and a benchmarking universal single-copy ortholog (BUSCO) score of 98%, representing one of the highest quality genomes to date for a member of the Pythonidae family. This assembly provides a valuable resource for studying snake-specific traits and evolutionary biology. Furthermore, it enables exploration of the molecular mechanisms underlying the remarkable cardiac and muscular adaptations in pythons, such as their ability to rapidly remodel their heart following feeding and resist muscular atrophy during prolonged fasting. These insights have potential applications in human health, particularly in the development of therapies targeting cardiac hypertrophy and muscular atrophy.<\/jats:p>","DOI":"10.1093\/g3journal\/jkaf197","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T08:28:24Z","timestamp":1756801704000},"source":"Crossref","is-referenced-by-count":1,"title":["Genome report: first whole genome assembly of\n                    <i>Python regius<\/i>\n                    (ball python), a model of extreme physiological and metabolic plasticity"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-5915","authenticated-orcid":false,"given":"Dakota R","family":"Hunt","sequence":"first","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Biochemistry, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Allen","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder , Boulder, CO 80309 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G","family":"Martin","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder , Boulder, CO 80309 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia N","family":"Feghali","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder , Boulder, CO 80309 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-937X","authenticated-orcid":false,"given":"Edward B","family":"Chuong","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder , Boulder, CO 80309 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A","family":"Leinwand","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder , Boulder, CO 80303 ,","place":["United States"]},{"name":"Department of Molecular, Cellular, and Developmental Biology, 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