Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity
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.
-
Morphological and genomic shifts in mole-rat queens increase fecundity but reduce skeletal integrityNCBI Gene Expression Omnibus, series accession, GSE152659.
-
Morphological and genomic shifts in mole-rat queens increase fecundity but reduce skeletal integrityNCBI Sequence Read Archive, BioProject accession number, PRJNA649596.
Article and author information
Author details
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
- George H Perry, Pennsylvania State University, United States
Version history
- Received: December 15, 2020
- Accepted: April 11, 2021
- Accepted Manuscript published: April 12, 2021 (version 1)
- 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
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)
Further reading
-
- Cell Biology
- Chromosomes and Gene Expression
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.
-
- Chromosomes and Gene Expression
- Developmental Biology
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.