1. Chromosomes and Gene Expression
  2. Evolutionary Biology

Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity

  1. Rachel A Johnston  Is a corresponding author
  2. Philippe Vullioud
  3. Jack Thorley
  4. Henry Kirveslahti
  5. Leyao Shen
  6. Sayan Mukherjee
  7. Courtney M Karner
  8. Tim Clutton-Brock
  9. Jenny Tung  Is a corresponding author
  1. Duke University, United States
  2. University of Cambridge, United Kingdom
  3. Duke University School of Medicine, United States
  4. University of Texas Southwestern Medical Center, United States
https://doi.org/10.7554/eLife.65760
Share this article
Cite this article
  1. Rachel A Johnston
  2. Philippe Vullioud
  3. Jack Thorley
  4. Henry Kirveslahti
  5. Leyao Shen
  6. Sayan Mukherjee
  7. Courtney M Karner
  8. Tim Clutton-Brock
  9. Jenny Tung
(2021)
Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity
eLife 10:e65760.
https://doi.org/10.7554/eLife.65760
  2. Download BibTeX
  3. Download .RIS

Abstract

In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding 'queen' status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also up-regulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.

Data availability

All RNA sequencing data generated during this study are available in the NCBI Gene Expression Omnibus (series accession GSE152659). ATAC-Seq data are available in the NCBI Sequence Read Archive (BioProject accession number PRJNA649596). μCT data from this study are available on MorphoSource (http://www.morphosource.org, project 1056). All code used for the study are available at https://github.com/rachelj98/MoleratBones.

The following data sets were generated

Article and author information

Author details

  1. Rachel A Johnston

    Department of Evolutionary Anthropology, Duke University, Durham, United States
    For correspondence
    racheljohnston7@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8965-1162

  2. Philippe Vullioud

    Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.

  3. Jack Thorley

    Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.

  4. Henry Kirveslahti

    Department of Statistical Science, Duke University, Durham, United States
    Competing interests
    No competing interests declared.

  5. Leyao Shen

    Department of Orthopaedic Surgery, Duke Orthopaedic Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, United States
    Competing interests
    No competing interests declared.

  6. Sayan Mukherjee

    Department of Statistical Science; Department of Computer Science; Department of Mathematics; Department of Bioinformatics & Biostatistics, Duke University, Durham, United States
    Competing interests
    No competing interests declared.

  7. Courtney M Karner

    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  8. Tim Clutton-Brock

    Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.

  9. Jenny Tung

    Evolutionary Anthropology, Biology, Duke University, Durham, NC, United States
    For correspondence
    jenny.tung@duke.edu
    Competing interests
    Jenny Tung, Jenny Tung is a Reviewing Editor at eLife..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0416-2958

Funding

European Research Council (294494)

  • Tim Clutton-Brock

National Institutes of Health (AR076325)

  • Courtney M Karner

National Institutes of Health (AR071967)

  • Courtney M Karner

European Research Council (742808)

  • Tim Clutton-Brock

Human Frontier Science Program (RGP0051-2017)

  • Sayan Mukherjee
  • Tim Clutton-Brock
  • Jenny Tung

National Science Foundation (IOS-7801004)

  • Jenny Tung

National Institutes of Health (F32HD095616)

  • Rachel A Johnston

Sloan Foundation Early Career Research Fellowship

  • Jenny Tung

Foerster-Bernstein Postdoctoral Fellowship

  • Rachel A Johnston

Natural Environment Research Council (Doctoral Training Program Grant)

  • Jack Thorley

North Carolina Biotechnology Center (2016-IDG-1013)

  • Jenny Tung

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

Ethics

Animal experimentation: Animals were deeply anesthetized with isoflurane and sacrificed with decapitation following USGS National Wildlife Health Center guidelines and under approval from the Animal Ethics Committee of the University of Pretoria (Permit #EC081-17).

Reviewing Editor

  1. George H Perry, Pennsylvania State University, United States

Version history

  1. Received: December 15, 2020
  2. Accepted: April 11, 2021
  3. Accepted Manuscript published: April 12, 2021 (version 1)
  4. Version of Record published: May 7, 2021 (version 2)

Copyright

© 2021, Johnston 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

  • 1,536
    Page views
  • 157
    Downloads
  • 7
    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. Rachel A Johnston
  2. Philippe Vullioud
  3. Jack Thorley
  4. Henry Kirveslahti
  5. Leyao Shen
  6. Sayan Mukherjee
  7. Courtney M Karner
  8. Tim Clutton-Brock
  9. Jenny Tung
(2021)
Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity
eLife 10:e65760.
https://doi.org/10.7554/eLife.65760

Categories and tags

Further reading

    1. Chromosomes and Gene Expression

    Single molecule analysis of CENP-A chromatin by high-speed atomic force microscopy

    Daniël P Melters, Keir C Neuman ... Yamini Dalal
    Research Article

    Chromatin accessibility is modulated in a variety of ways to create open and closed chromatin states, both of which are critical for eukaryotic gene regulation. At the single molecule level, how accessibility is regulated of the chromatin fiber composed of canonical or variant nucleosomes is a fundamental question in the field. Here, we developed a single-molecule tracking method where we could analyze thousands of canonical H3 and centromeric variant nucleosomes imaged by high-speed atomic force microscopy. This approach allowed us to investigate how changes in nucleosome dynamics in vitro inform us about transcriptional potential in vivo. By high-speed atomic force microscopy, we tracked chromatin dynamics in real time and determined the mean square displacement and diffusion constant for the variant centromeric CENP-A nucleosome. Furthermore, we found that an essential kinetochore protein CENP-C reduces the diffusion constant and mobility of centromeric nucleosomes along the chromatin fiber. We subsequently interrogated how CENP-C modulates CENP-A chromatin dynamics in vivo. Overexpressing CENP-C resulted in reduced centromeric transcription and impaired loading of new CENP-A molecules. From these data, we speculate that factors altering nucleosome mobility in vitro, also correspondingly alter transcription in vivo. Subsequently, we propose a model in which variant nucleosomes encode their own diffusion kinetics and mobility, and where binding partners can suppress or enhance nucleosome mobility.

    1. Cell Biology
    2. Chromosomes and Gene Expression

    The kleisin subunit controls the function of C. elegans meiotic cohesins by determining the mode of DNA binding and differential regulation by SCC-2 and WAPL-1

    Maikel Castellano-Pozo, Georgios Sioutas ... Enrique Martinez-Perez
    Short Report Updated

    The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in Caenorhabditis elegans. How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin–DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes.

    1. Chromosomes and Gene Expression
    2. Developmental Biology

    lncRNA read-through regulates the BX-C insulator Fub-1

    Airat Ibragimov, Xin Yang Bing ... Paul Schedl
    Research Article Updated

    Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) Fub-1 boundary is segmentally regulated by its own lncRNA. The Fub-1 boundary is located between the Ultrabithorax (Ubx) gene and the bxd/pbx regulatory domain, which is responsible for regulating Ubx expression in parasegment PS6/segment A1. Fub-1 consists of two hypersensitive sites, HS1 and HS2. HS1 is an insulator while HS2 functions primarily as an lncRNA promoter. To activate Ubx expression in PS6/A1, enhancers in the bxd/pbx domain must be able to bypass Fub-1 blocking activity. We show that the expression of the Fub-1 lncRNAs in PS6/A1 from the HS2 promoter inactivates Fub-1 insulating activity. Inactivation is due to read-through as the HS2 promoter must be directed toward HS1 to disrupt blocking.