A recurrent regulatory change underlying altered expression and Wnt response of the stickleback armor plates gene EDA

  1. Natasha M O'Brown
  2. Brian R Summers
  3. Felicity C Jones
  4. Shannon D Brady
  5. David M Kingsley  Is a corresponding author
  1. Stanford University School of Medicine, United States
  2. General Practice Dentistry, United States
  3. Max Planck Institute for Developmental Biology, Germany
  4. Howard Hughes Medical Institute, Stanford University School of Medicine, United States

Abstract

Armor plate changes in sticklebacks are a classic example of repeated adaptive evolution. Previous studies identified ectodysplasin (EDA) gene as the major locus controlling recurrent plate loss in freshwater fish, though the causative DNA alterations were not known. Here we show that freshwater EDA alleles have cis-acting regulatory changes that reduce expression in developing plates and spines. An identical T->G base pair change is found in EDA enhancers of divergent low-plated fish. Recreation of the T->G change in a marine enhancer strongly reduces expression in posterior armor plates. Bead implantation and cell culture experiments show that Wnt signaling strongly activates the marine EDA enhancer, and the freshwater T->G change reduces Wnt responsiveness. Thus parallel evolution of low-plated sticklebacks has occurred through a shared DNA regulatory change, which reduces the sensitivity of an EDA enhancer to Wnt signaling, and alters expression in developing armor plates while preserving expression in other tissues.

Article and author information

Author details

  1. Natasha M O'Brown

    Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brian R Summers

    General Practice Dentistry, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Felicity C Jones

    Friedrich Miescher Laboratory, Max Planck Institute for Developmental Biology, Tuebingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Shannon D Brady

    Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. David M Kingsley

    Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    For correspondence
    kingsley@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#13834) of Stanford University, in animal facilities accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).

Version history

  1. Received: October 23, 2014
  2. Accepted: January 26, 2015
  3. Accepted Manuscript published: January 28, 2015 (version 1)
  4. Version of Record published: February 17, 2015 (version 2)

Copyright

© 2015, O'Brown 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

  • 3,993
    views
  • 650
    downloads
  • 90
    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. Natasha M O'Brown
  2. Brian R Summers
  3. Felicity C Jones
  4. Shannon D Brady
  5. David M Kingsley
(2015)
A recurrent regulatory change underlying altered expression and Wnt response of the stickleback armor plates gene EDA
eLife 4:e05290.
https://doi.org/10.7554/eLife.05290

Share this article

https://doi.org/10.7554/eLife.05290

Further reading

    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation
    Rajan M Thomas, Matthew C Pahl ... Andrew D Wells
    Research Article

    Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (Ikzf1). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While Ikzf1-Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.