The evolution of hominin bipedalism in two steps
Bipedalism is a human-defining trait<sup>1-3</sup>. It is made possible by the familiar, bowl-shaped pelvis, whose short, wide iliac blades curve along the sides of the body to stabilize walking and support internal organs and a large-brained, broad-shouldered baby<sup>4-6</sup>. The ilium changes compared with living primates are an evolutionary novelty<sup>7</sup>. However, how this evolution came about remains unknown. Here, using a multifaceted histological, comparative genomic and functional genomic approach, we identified the developmental bases of the morphogenetic shifts in the human pelvis that made bipedalism possible. First, we observe that the human ilium cartilage growth plate underwent a heterotopic shift, residing perpendicular to the orientation present in other primate (and mouse) ilia. Second, we observe heterochronic and heterotopic shifts in ossification that are unlike those in non-human primate ilia or human long bones. Ossification initiates posteriorly, resides externally with fibroblast (and perichondral) cells contributing to osteoblasts, and is delayed compared with other bones in humans and with primate ilia. Underlying these two shifts are regulatory changes in an integrated chondrocyte-perichondral-osteoblast pathway, involving complex hierarchical interactions between SOX9-ZNF521-PTH1R and RUNX2-FOXP1/2. These innovations facilitated further growth of the human pelvis and the unique formation of the ilium among primates.
Authors
- Ian C. Simcock
- Jakob Höppner (ORCID: https://orcid.org/0000-0001-9908-2066)
- Terence D. Capellini (ORCID: https://orcid.org/0000-0003-3842-8478)
- Nadia B. Fröbisch (ORCID: https://orcid.org/0000-0002-1019-9733)
- Alistair Calder (ORCID: https://orcid.org/0000-0001-8335-299X)
- Stephanie L. Baumgart (ORCID: https://orcid.org/0000-0001-9534-7389)
- Owen J. Arthurs (ORCID: https://orcid.org/0000-0003-1213-3516)
- April M. Craft (ORCID: https://orcid.org/0000-0002-4423-8008)
- Vivien Bothe (ORCID: https://orcid.org/0000-0002-3402-1809)
- Gayani Senevirathne (ORCID: https://orcid.org/0000-0001-6704-9691)
- Peishu Li (ORCID: https://orcid.org/0000-0002-8299-9166)
- Niamh C. Nowlan (ORCID: https://orcid.org/0000-0002-9083-6279)
- Harald Jüppner
- Ian A. Glass (ORCID: https://orcid.org/0000-0001-6762-8407)
- Daniel Richard (ORCID: https://orcid.org/0000-0001-8568-9473)
- M. Fabbri
- Naomi Freilich
- Serena C Fernandopulle
- Anika Liv Christensen
Institutions
- University College Dublin (IE)
- Broad Institute (US)
- Boston Children's Hospital (US)
- Museum für Naturkunde (DE)
- Harvard University (US)
- Johns Hopkins University (US)
- University of Washington (US)
- Johns Hopkins Medicine (US)
- Great Ormond Street Hospital (GB)
- Harvard University Press (US)
- University of Florida (US)
- Massachusetts General Hospital (US)
- Ohio University (US)
- Evolutionary Genomics (United States) (US)
- Harvard Stem Cell Institute (US)
- University College London (GB)
- Florida College (US)
- Stanford University (US)
Publication Details
- Journal
- Nature
- Published
- 2025-08-27
- DOI
- https://doi.org/10.1038/s41586-025-09399-9
- Citations
- 13
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 12.17