Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature Communications
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. nature communications
  3. articles
  4. article
Evolution of limb and digit identity genes since the tetrapod ancestor
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 27 May 2026

Evolution of limb and digit identity genes since the tetrapod ancestor

  • Wen Kang  ORCID: orcid.org/0000-0002-1024-77821,2,
  • Ji-Feng Fei3,4,
  • Cong Liang5,
  • Günter Wagner  ORCID: orcid.org/0000-0002-3097-002X6,7,8,9 &
  • …
  • Qi Zhou  ORCID: orcid.org/0000-0002-7419-20471,2,10,11 

Nature Communications (2026) Cite this article

  • 413 Accesses

  • 7 Altmetric

  • Metrics details

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

  • Evolutionary biology
  • Evolutionary developmental biology
  • Molecular evolution

Abstract

Natural selection has sculpted tetrapod limbs and digits into a tremendous morphological diversity, but the underlying developmental mechanism remains unclear. This leads to an enduring debate concerning the identity of the three digits of bird wing. Here we use comparative digit transcriptomics across six tetrapod species to examine gene expression signatures of digit evolution. Here we show that the avian wing digits are homologous to reptilian forelimb digits 1,3,4. We find that birds uniquely increase fore-hindlimb transcriptome divergence during development, relaxing constraints and facilitating wing and foot digit specialization. We identify many limb- or digit- identity associated genes that have a biased expression between fore- or hind-limb, or toward specific digits. There are more limb and digit biased genes among the avian lineages than in other tetrapod lineages. Our work reveals ancient regulatory networks that maintain limb and digit molecular identity through persistent differential expression. We also show that this conserved network does not preclude independent digit evolution, especially when developmental constraints are reduced.

Similar content being viewed by others

Low morphological disparity and decelerated rate of limb size evolution close to the origin of birds

Article 05 June 2023

Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

Article Open access 16 July 2025

Proximal phalanges of digit 1 have different identities in the forelimbs and hindlimbs of the mouse

Article Open access 27 October 2025

Acknowledgements

We thank Jingwen Yang for providing advice and guidance on the application of TreeExp.

Funding

Qi Zhou is supported by the National Key Research and Development Program of China (2023YFA1800500, 2024YFA1802500), National Natural Science Foundation of China (32170415) and Fundamental Research Funds for the Central Universities (226-2024-00055) from Zhejiang University.

Author information

Authors and Affiliations

  1. Center for Reproductive Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China

    Wen Kang & Qi Zhou

  2. Center for Evolutionary & Organismal Biology, Zhejiang University, Hangzhou, China

    Wen Kang & Qi Zhou

  3. Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China

    Ji-Feng Fei

  4. School of Medicine, South China University of Technology, Guangzhou, Guangdong, China

    Ji-Feng Fei

  5. Center for Applied Mathematics, Tianjin University, Tianjin, China

    Cong Liang

  6. Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA

    Günter Wagner

  7. Yale Systems Biology Institute, Yale University, New Haven, CT, USA

    Günter Wagner

  8. Department of Evolutionary Biology, University of Vienna, Vienna, Austria

    Günter Wagner

  9. Hagler Institute for Advanced Study, Texas A&M University, College Station, TX, USA

    Günter Wagner

  10. Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China

    Qi Zhou

  11. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China

    Qi Zhou

Authors
  1. Wen Kang
    View author publications

    Search author on:PubMed Google Scholar

  2. Ji-Feng Fei
    View author publications

    Search author on:PubMed Google Scholar

  3. Cong Liang
    View author publications

    Search author on:PubMed Google Scholar

  4. Günter Wagner
    View author publications

    Search author on:PubMed Google Scholar

  5. Qi Zhou
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Günter Wagner or Qi Zhou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information (download PDF )

Description of Additional Supplementary Files (download PDF )

Supplementary Data 1-10 (download XLSX )

Reporting Summary (download PDF )

Transparent Peer Review file (download PDF )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, W., Fei, JF., Liang, C. et al. Evolution of limb and digit identity genes since the tetrapod ancestor. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73821-7

Download citation

  • Received: 28 November 2025

  • Accepted: 19 May 2026

  • Published: 27 May 2026

  • DOI: https://doi.org/10.1038/s41467-026-73821-7

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Videos
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Aims & Scope
  • Editors
  • Journal Information
  • Open Access Fees and Funding
  • Calls for Papers
  • Editorial Values Statement
  • Journal Metrics
  • Editors' Highlights
  • Contact
  • Editorial policies
  • Top Articles

Publish with us

  • For authors
  • For Reviewers
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Nature Communications (Nat Commun)

ISSN 2041-1723 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing