Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis

Abstract

After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of Xenopus laevis, an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in predicted enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid X. tropicalis and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.

Data availability

All data and analysis files are available with no restrictions on access. Sequencing data are available in the Gene Expression Omnibus (GEO) under accession number GSE207027. Code and auxiliary data files are available on Github, github.com/MTLeeLab/xl-zga. Additional data files including chromosome alignments are available at OSF, osf.io/ct6g8/

The following data sets were generated
    1. Phelps WA
    2. Lee MT
    (2022) Xenopus MZT
    OSF, DOI 10.17605/OSF.IO/CT6G8.
The following previously published data sets were used

Article and author information

Author details

  1. Wesley A Phelps

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4056-2345
  2. Matthew D Hurton

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Taylor N Ayers

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0680-0773
  4. Anne E Carlson

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2724-1325
  5. Joel C Rosenbaum

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Miler T Lee

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    miler@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0933-0551

Funding

National Institutes of Health (R35GM137973)

  • Miler T Lee

March of Dimes Foundation (5-FY16-307)

  • Miler T Lee

Samuel and Emma Winters Foundation

  • Miler T Lee

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

Ethics

Animal experimentation: All animal procedures were conducted under the supervision and approval of the Institutional Animal Care and Use Committee at the University of Pittsburgh under protocol #21120500.

Copyright

© 2023, Phelps 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

  • 778
    views
  • 126
    downloads
  • 3
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Wesley A Phelps
  2. Matthew D Hurton
  3. Taylor N Ayers
  4. Anne E Carlson
  5. Joel C Rosenbaum
  6. Miler T Lee
(2023)
Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis
eLife 12:e83952.
https://doi.org/10.7554/eLife.83952

Share this article

https://doi.org/10.7554/eLife.83952

Further reading

    1. Developmental Biology
    2. Physics of Living Systems
    Fridtjof Brauns, Nikolas H Claussen ... Boris I Shraiman
    Research Article

    Shape changes of epithelia during animal development, such as convergent extension, are achieved through the concerted mechanical activity of individual cells. While much is known about the corresponding large-scale tissue flow and its genetic drivers, fundamental questions regarding local control of contractile activity on the cellular scale and its embryo-scale coordination remain open. To address these questions, we develop a quantitative, model-based analysis framework to relate cell geometry to local tension in recently obtained time-lapse imaging data of gastrulating Drosophila embryos. This analysis systematically decomposes cell shape changes and T1 rearrangements into internally driven, active, and externally driven, passive, contributions. Our analysis provides evidence that germ band extension is driven by active T1 processes that self-organize through positive feedback acting on tensions. More generally, our findings suggest that epithelial convergent extension results from the controlled transformation of internal force balance geometry which combines the effects of bottom-up local self-organization with the top-down, embryo-scale regulation by gene expression.

    1. Computational and Systems Biology
    2. Developmental Biology
    Rosalío Reyes, Arthur D Lander, Marcos Nahmad
    Research Article Updated

    Understanding the principles underlying the design of robust, yet flexible patterning systems is a key problem in developmental biology. In the Drosophila wing, Hedgehog (Hh) signaling determines patterning outputs using dynamical properties of the Hh gradient. In particular, the pattern of collier (col) is established by the steady-state Hh gradient, whereas the pattern of decapentaplegic (dpp), is established by a transient gradient of Hh known as the Hh overshoot. Here, we use mathematical modeling to suggest that this dynamical interpretation of the Hh gradient results in specific robustness and precision properties. For instance, the location of the anterior border of col, which is subject to self-enhanced ligand degradation is more robustly specified than that of dpp to changes in morphogen dosage, and we provide experimental evidence of this prediction. However, the anterior border of dpp expression pattern, which is established by the overshoot gradient is much more precise to what would be expected by the steady-state gradient. Therefore, the dynamical interpretation of Hh signaling offers tradeoffs between robustness and precision to establish tunable patterning properties in a target-specific manner.