Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity
- Duke University, United States
- University of Cambridge, United Kingdom
- Duke University School of Medicine, United States
- University of Texas Southwestern Medical Center, United States
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.
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Morphological and genomic shifts in mole-rat queens increase fecundity but reduce skeletal integrityNCBI Gene Expression Omnibus, series accession, GSE152659.
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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).
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.
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Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity
eLife 10:e65760.
https://doi.org/10.7554/eLife.65760
Further reading
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During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme – the senescence-associated secretory phenotype (SASP) – driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here, we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin re-organisation during senescence, is also required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of innate immune signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. We show that HMGA1 is also required for cytoplasmic chromatin fragment formation. Together these data suggest that re-organisation of heterochromatin is involved in altered structural integrity of the nuclear periphery during senescence, and that this can lead to activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP.
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- Chromosomes and Gene Expression
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Gene regulation is essential for life and controlled by regulatory DNA. Mutations can modify the activity of regulatory DNA, and also create new regulatory DNA, a process called regulatory emergence. Non-regulatory and regulatory DNA contain motifs to which transcription factors may bind. In prokaryotes, gene expression requires a stretch of DNA called a promoter, which contains two motifs called –10 and –35 boxes. However, these motifs may occur in both promoters and non-promoter DNA in multiple copies. They have been implicated in some studies to improve promoter activity, and in others to repress it. Here, we ask whether the presence of such motifs in different genetic sequences influences promoter evolution and emergence. To understand whether and how promoter motifs influence promoter emergence and evolution, we start from 50 ‘promoter islands’, DNA sequences enriched with –10 and –35 boxes. We mutagenize these starting ‘parent’ sequences, and measure gene expression driven by 240,000 of the resulting mutants. We find that the probability that mutations create an active promoter varies more than 200-fold, and is not correlated with the number of promoter motifs. For parent sequences without promoter activity, mutations created over 1500 new –10 and –35 boxes at unique positions in the library, but only ~0.3% of these resulted in de-novo promoter activity. Only ~13% of all –10 and –35 boxes contribute to de-novo promoter activity. For parent sequences with promoter activity, mutations created new –10 and –35 boxes in 11 specific positions that partially overlap with preexisting ones to modulate expression. We also find that –10 and –35 boxes do not repress promoter activity. Overall, our work demonstrates how promoter motifs influence promoter emergence and evolution. It has implications for predicting and understanding regulatory evolution, de novo genes, and phenotypic evolution.
