1. Evolutionary Biology

Computed tomography shows high fracture prevalence among physically active forager-horticulturalists with high fertility

  1. Jonathan Stieglitz  Is a corresponding author
  2. Benjamin C Trumble
  3. HORUS Study Team
  4. Caleb Finch
  5. Dong Li
  6. Matthew J Budoff
  7. Hillard Kaplan
  8. Michael Gurven
  1. Universite Toulouse 1 Capitole, France
  2. Arizona State University, United States
  3. University of Southern California, United States
  4. Emory University, United States
  5. University of California, Los Angeles, United States
  6. Chapman University, United States
  7. University of California, Santa Barbara, United States
https://doi.org/10.7554/eLife.48607
Share this article
Cite this article
  1. Jonathan Stieglitz
  2. Benjamin C Trumble
  3. HORUS Study Team
  4. Caleb Finch
  5. Dong Li
  6. Matthew J Budoff
  7. Hillard Kaplan
  8. Michael Gurven
(2019)
Computed tomography shows high fracture prevalence among physically active forager-horticulturalists with high fertility
eLife 8:e48607.
https://doi.org/10.7554/eLife.48607
  2. Download BibTeX
  3. Download .RIS

Abstract

Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on inactivity to explain skeletal fragility. Minimal BMD differences exist between Tsimane and American men, suggesting that systemic factors other than fertility (e.g. diet) do not easily explain Tsimane women's lower BMD. Tsimane fracture prevalence is also higher versus Americans. Lower BMD increases Tsimane fracture risk, but only for women, suggesting a role of weak bone in women's fracture etiology. Our results highlight the role of sex-specific mechanisms underlying skeletal fragility that operate long before menopause.

Data availability

The data that support the findings of this study are available on Dryad (http://dx.doi.org/10.5061/dryad.rf0g0md).

The following data sets were generated

Article and author information

Author details

  1. Jonathan Stieglitz

    Institute for Advanced Study in Toulouse, Universite Toulouse 1 Capitole, Toulouse, France
    For correspondence
    jonathan.stieglitz@iast.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5985-9643

  2. Benjamin C Trumble

    Arizona State University, Tempe, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. HORUS Study Team

  4. Caleb Finch

    University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7617-3958

  5. Dong Li

    Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Matthew J Budoff

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Hillard Kaplan

    Chapman University, Orange, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Michael Gurven

    University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01AG024119)

  • Jonathan Stieglitz
  • Benjamin C Trumble
  • Caleb Finch
  • Hillard Kaplan
  • Michael Gurven

Arizona State University

  • Benjamin C Trumble

University of California, Santa Barbara

  • Michael Gurven

Agence Nationale de la Recherche (ANR-17-EURE-0010)

  • Jonathan Stieglitz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Institutional IRB approval was granted by UNM (HRRC # 07-157) and UCSB (# 3-16-0766), as was informed consent at three levels: (1) Tsimane government that oversees research projects, (2) village leadership and (3) study participants.

Reviewing Editor

  1. Diethard Tautz, Max-Planck Institute for Evolutionary Biology, Germany

Version history

  1. Received: May 20, 2019
  2. Accepted: August 14, 2019
  3. Accepted Manuscript published: August 16, 2019 (version 1)
  4. Version of Record published: September 4, 2019 (version 2)
  5. Version of Record updated: September 9, 2019 (version 3)

Copyright

© 2019, Stieglitz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 847
    Page views
  • 95
    Downloads
  • 15
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jonathan Stieglitz
  2. Benjamin C Trumble
  3. HORUS Study Team
  4. Caleb Finch
  5. Dong Li
  6. Matthew J Budoff
  7. Hillard Kaplan
  8. Michael Gurven
(2019)
Computed tomography shows high fracture prevalence among physically active forager-horticulturalists with high fertility
eLife 8:e48607.
https://doi.org/10.7554/eLife.48607

Categories and tags

Research organism

Further reading

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Diverse evolutionary pathways challenge the use of collateral sensitivity as a strategy to suppress resistance

    Rebecca EK Mandt, Madeline R Luth ... Amanda K Lukens
    Research Article

    Drug resistance remains a major obstacle to malaria control and eradication efforts, necessitating the development of novel therapeutic strategies to treat this disease. Drug combinations based on collateral sensitivity, wherein resistance to one drug causes increased sensitivity to the partner drug, have been proposed as an evolutionary strategy to suppress the emergence of resistance in pathogen populations. In this study, we explore collateral sensitivity between compounds targeting the Plasmodium dihydroorotate dehydrogenase (DHODH). We profiled the cross-resistance and collateral sensitivity phenotypes of several DHODH mutant lines to a diverse panel of DHODH inhibitors. We focus on one compound, TCMDC-125334, which was active against all mutant lines tested, including the DHODH C276Y line, which arose in selections with the clinical candidate DSM265. In six selections with TCMDC-125334, the most common mechanism of resistance to this compound was copy number variation of the dhodh locus, although we did identify one mutation, DHODH I263S, which conferred resistance to TCMDC-125334 but not DSM265. We found that selection of the DHODH C276Y mutant with TCMDC-125334 yielded additional genetic changes in the dhodh locus. These double mutant parasites exhibited decreased sensitivity to TCMDC-125334 and were highly resistant to DSM265. Finally, we tested whether collateral sensitivity could be exploited to suppress the emergence of resistance in the context of combination treatment by exposing wildtype parasites to both DSM265 and TCMDC-125334 simultaneously. This selected for parasites with a DHODH V532A mutation which were cross-resistant to both compounds and were as fit as the wildtype parent in vitro. The emergence of these cross-resistant, evolutionarily fit parasites highlights the mutational flexibility of the DHODH enzyme.

    1. Evolutionary Biology
    2. Neuroscience

    Diversity and evolution of cerebellar folding in mammals

    Katja Heuer, Nicolas Traut ... Roberto Toro
    Research Article

    The process of brain folding is thought to play an important role in the development and organisation of the cerebrum and the cerebellum. The study of cerebellar folding is challenging due to the small size and abundance of its folia. In consequence, little is known about its anatomical diversity and evolution. We constituted an open collection of histological data from 56 mammalian species and manually segmented the cerebrum and the cerebellum. We developed methods to measure the geometry of cerebellar folia and to estimate the thickness of the molecular layer. We used phylogenetic comparative methods to study the diversity and evolution of cerebellar folding and its relationship with the anatomy of the cerebrum. Our results show that the evolution of cerebellar and cerebral anatomy follows a stabilising selection process. We observed 2 groups of phenotypes changing concertedly through evolution: a group of 'diverse' phenotypes - varying over several orders of magnitude together with body size, and a group of 'stable' phenotypes varying over less than 1 order of magnitude across species. Our analyses confirmed the strong correlation between cerebral and cerebellar volumes across species, and showed in addition that large cerebella are disproportionately more folded than smaller ones. Compared with the extreme variations in cerebellar surface area, folial anatomy and molecular layer thickness varied only slightly, showing a much smaller increase in the larger cerebella. We discuss how these findings could provide new insights into the diversity and evolution of cerebellar folding, the mechanisms of cerebellar and cerebral folding, and their potential influence on the organisation of the brain across species.

    1. Developmental Biology
    2. Evolutionary Biology

    The Natural History of Model Organisms: Amphioxus as a model to study the evolution of development in chordates

    Salvatore D'Aniello, Stephanie Bertrand, Hector Escriva
    Feature Article

    Cephalochordates and tunicates represent the only two groups of invertebrate chordates, and extant cephalochordates – commonly known as amphioxus or lancelets – are considered the best proxy for the chordate ancestor, from which they split around 520 million years ago. Amphioxus has been an important organism in the fields of zoology and embryology since the 18th century, and the morphological and genomic simplicity of cephalochordates (compared to vertebrates) makes amphioxus an attractive model for studying chordate biology at the cellular and molecular levels. Here we describe the life cycle of amphioxus, and discuss the natural histories and habitats of the different species of amphioxus. We also describe their use as laboratory animal models, and discuss the techniques that have been developed to study different aspects of amphioxus.