{
  "abstract": "Vertebrate limb bones grow at different rates within and between species to achieve a striking variety of proportions and functions. However, most coding mutations that alter bone growth in mice and humans affect the entire skeleton, pointing to cis-regulatory modularity as the primary mechanism to diversify proportion. In a search for causative loci, we previously identified 1,755 disproportionately differentially expressed genes associated with the extreme hindlimb elongation in bipedal jerboas, Jaculus jaculus, compared to laboratory mice. We then took a focused approach to identify putative cis-regulatory elements near select candidate genes in a highly fragmented draft Jaculus jaculus genome assembly. We identified an ATAC-seq peak near Shox2 that was reproducible in jerboa metatarsals and not in radius/ulna. Shox2 gained a novel expression domain in jerboa metatarsals and is both necessary and sufficient to modulate mouse limb bone length. This 139 bp putative enhancer in the jerboa genome centers on a ~1 kb deletion of sequence found broadly throughout placental mammals. Here, we show that replicating the deletion and replacement with the 139 bp jerboa sequence in mice causes no detected phenotype. A genome-wide analysis of our ATAC-seq data using a high-quality Jaculus jaculus genome assembly replicated the peak called at this location but also identified 7,445 peaks that are similarly reproducible in metatarsals and not in radius/ulna. Certainly not all of these peaks are causative, but it is likely that many small-effect mutations diversified proportion. It is therefore crucial to apply unbiased filters to genome-wide analyses and to not assume that the few historically favored genes will have the largest effect.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, San Diego"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "G. Guerrero"
    },
    {
      "name": "A. Y. Liu"
    },
    {
      "name": "A. J. Weitzel"
    },
    {
      "name": "E. Gacasan"
    },
    {
      "name": "M. Hiller"
    },
    {
      "name": "R. Sah"
    },
    {
      "affs": [
        0
      ],
      "name": "K. L. Cooper"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0b2kjyq7xgre4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752424",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752424v1.full",
  "id": "0b2kjyq7xgre4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752424v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "evolutionary biology"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7213675206",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752424v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0b2kjyq7xgre4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:11Z",
      "native_id": "10.64898/2026.09.17.752424",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752424v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:evolutionary biology",
      "subfield": "evolutionary-biology"
    }
  ],
  "title": "A putative cis-regulatory element near Shox2 in the jerboa genome (Jaculus jaculus) is not sufficient to alter mouse limb bone lengths",
  "title_text": "A putative cis-regulatory element near Shox2 in the jerboa genome (Jaculus jaculus) is not sufficient to alter mouse limb bone lengths",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:11Z",
  "url": "https://research.draconitic.com/paper/0b2kjyq7xgre4",
  "venue": "bioRxiv",
  "versions": []
}