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INSIG1 parallel substitution drives lipid/sterol metabolic plasticity mediating desert adaptation in ungulates
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  • Published: 12 January 2026

INSIG1 parallel substitution drives lipid/sterol metabolic plasticity mediating desert adaptation in ungulates

  • Xinmei Li1 na1,
  • Ziyi He2 na1,
  • Anguo Liu1,
  • Fanxin Meng1,
  • Xiao Zhang1,
  • Nana Li2,
  • Huan Liu2,
  • Yuyi Lu1,
  • Zhipei Wu1,
  • Huimei Fan1,
  • Xixi Yan1,
  • Nange Ma1,
  • Zhenyu Wei1,
  • Wei Wang1,
  • Xixi He1,
  • Kunyu Ma1,
  • Yu Jiang  ORCID: orcid.org/0000-0003-4821-35851,
  • Chao Tong  ORCID: orcid.org/0000-0001-5202-55073,
  • Bo Xia  ORCID: orcid.org/0000-0002-4041-91511,2 &
  • …
  • Yu Wang  ORCID: orcid.org/0000-0001-5719-29611,4 

Communications Biology , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Conservation genomics
  • Molecular evolution

Abstract

Desert ungulates, such as Camelus bactrianus and Hippotraginae antelopes, exhibit extraordinary adaptation to extreme environment. Deciphering these genetic adaptations is critical for understanding evolutionary resilience under climate change. Here, we generate a chromosome-level genome for domestic Bactrian camel and integrate comparative genomics analyses to uncover genomic adaptation in arid-desert ungulates. We find elevated molecular evolution rates with intensified positive selection among desert-adapted lineages. Convergent positively selected genes are mainly involved in energy metabolism, and ion transport and homeostasis. In addition, we identify further evidence reveals numerous parallel amino acid substitution genes associated with lipid/sterol metabolism, particularly cholesterol biosynthesis. Cross-species metabolomics reveal lower steroid-lipid levels in fasting camel serum, suggesting that genetic adaptation promotes metabolic trade-offs for desert survival. INSIG1 involved in cholesterol biosynthesis process emerge as a key candidate. Functional validation reveals that the INSIG1 mutation enhances lipid synthesis in energy-rich hepatocytes and promotes lipolysis during fasting in genome-edited male mice. Altogether, these findings highlight lipid/sterol plasticity as a cornerstone of desert adaptation, providing insights into breeding drought-resistant livestock and advancing therapeutic strategies for human metabolic disorders.

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Data availability

The genome data generated in this study have been submitted to the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number: BioProject ID: PRJNA1158569; BioSample ID: SAMN43543267. Submitted GenBank assembly GCA_048773025.1 in this study has now been listed on the NCBI website as NCBI RefSeq assembly GCF_048773025.1 Addgene ID: 250155, 250158, 250159 The transcriptome data of mice has also been uploaded to NCBI with accession number: SRP620610. Detailed information can be found in the Supplementary Data 23. Numerical source data for graphs and charts can be found in Supplementary Data 4–23. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

The in-house Perl scripts have been uploaded to github (https://github.com/1221li/comparative-genome.git).

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Acknowledgements

We thank the High-Performance Computing Center (HPC) of Northwest A&F University (NWAFU) for providing computing resources. We thank Mallory Eckstut, PhD for editing the English text of a draft of this manuscript. This work was supported by grants from National Key Research and Development Program of China (2021YFF1001000), and Postdoctoral Innovative Talents Support Program of China (BX20200282), and National Natural Science Foundation of China (Grant No. 32570633).

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Author notes
  1. These authors contributed equally: Xinmei Li, Ziyi He.

Authors and Affiliations

  1. Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China

    Xinmei Li, Anguo Liu, Fanxin Meng, Xiao Zhang, Yuyi Lu, Zhipei Wu, Huimei Fan, Xixi Yan, Nange Ma, Zhenyu Wei, Wei Wang, Xixi He, Kunyu Ma, Yu Jiang, Bo Xia & Yu Wang

  2. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China

    Ziyi He, Nana Li, Huan Liu & Bo Xia

  3. School of Life Sciences, Arizona State University, Tempe, AZ, USA

    Chao Tong

  4. Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi, China

    Yu Wang

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Contributions

Conceptualization: Yu Wang, Bo Xia, Chao Tong Formal Analysis: Xinmei Li Investigation: Xinmei Li, Ziyi He, Anguo Liu, Fanxin Meng, Xiao Zhang, Huan Liu, Nana Li, Yuyi Lu, Zhipei Wu, Huimei Fan, Xixi Yan, Nange Ma, Zhenyu Wei, Wei Wang, Xixi He, Kunyu Ma, Yu Jiang Experimental Verification: Bo Xia, Ziyi He, Xiao Zhang, Huan Liu, Nana Li Funding Acquisition: Yu Wang Supervision: Yu Wang Visualization: Xinmei Li, Ziyi He, Anguo Liu, Fanxin Meng, Xiao Zhang, Huan Liu, Nana Li Writing – Original Draft Preparation: Xinmei Li Writing – Review & Editing: Yu Wang, Bo Xia, Chao Tong.

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Correspondence to Chao Tong, Bo Xia or Yu Wang.

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Li, X., He, Z., Liu, A. et al. INSIG1 parallel substitution drives lipid/sterol metabolic plasticity mediating desert adaptation in ungulates. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09523-z

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  • Received: 30 April 2025

  • Accepted: 05 January 2026

  • Published: 12 January 2026

  • DOI: https://doi.org/10.1038/s42003-026-09523-z

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