{
  "abstract": "The turquoise karst lakes of China’s Jiuzhaigou Nature Reserve harbor among the highest natural calcium concentrations known in freshwater, around threefold higher than adjacent rivers. Yet the Jialing fish ( Schizopygopsis kialingensis ) thrives there with serum calcium levels indistinguishable from river-dwelling conspecifics. We show that this calcium tolerance arose through evolutionary loss of vitamin D signaling. Lake and river populations diverged ∼410,000 years ago. Gill transcriptomics revealed >90% suppression of vitamin D receptor b ( vdrb ) and 99% reduction of its downstream calcium transporter calb2a in lake fish. Zebrafish knockout of either gene enhanced survival under hypercalcemia. We traced this suppression to specific mutations in a vdrb enhancer that reduce its activity. These findings reveal that regulatory dismantling of a canonical endocrine pathway can drive vertebrate adaptation to extreme environments, providing a clear example of how cis-regulatory evolution can drive ecological adaptation.",
  "abstract_shown": true,
  "affiliations": [
    "College of Life Sciences, Northwest Normal University, Lanzhou 730000, China.",
    "Jiuzhaigou Administration Bureau, Jiuzhaigou 623407, China.",
    "Gansu Key Laboratory of Cold Water Fishes Germplasm Resources and Genetics Breeding, Gansu Fishers Research Institute, Lanzhou 730000, China.",
    "Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.",
    "Gansu Pharmaceutical Group, Lanzhou 730000, China."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nan Zhang",
      "orcid": "0009-0002-6559-2644"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongsen Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianbin Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianhao Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huilin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongsheng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingyun Chen",
      "orcid": "0000-0002-5031-8653"
    },
    {
      "affs": [
        1
      ],
      "name": "Weiyang Xiao"
    },
    {
      "affs": [
        2
      ],
      "name": "Tai Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Aaron J. W Hsueh",
      "orcid": "0000-0002-3500-2124"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Jianzhen Li",
      "orcid": "0009-0004-4747-6249"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4a7r0zqhrzn59.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeg8398",
  "fulltext_url": null,
  "id": "4a7r0zqhrzn59",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeg8398",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Evolution and Genetic Dynamics"
    ]
  ],
  "openalex": "W7220862889",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/4a7r0zqhrzn59.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeg8398",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeg8398"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Evolution and Genetic Dynamics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Cis-regulatory inactivation of vitamin D signaling confers extreme calcium tolerance in Jialing fish",
  "title_text": "Cis-regulatory inactivation of vitamin D signaling confers extreme calcium tolerance in Jialing fish",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/4a7r0zqhrzn59",
  "venue": "Science Advances",
  "versions": []
}