Silencing of transposable elements may not be a major driver of regulatory evolution in primate iPSCs

  1. Michelle C Ward  Is a corresponding author
  2. Siming Zhao
  3. Kaixuan Luo
  4. Bryan J Pavlovic
  5. Mohammad M Karimi
  6. Matthew Stephens
  7. Yoav Gilad  Is a corresponding author
  1. University of Chicago, United States
  2. Imperial College London, United Kingdom

Abstract

Transposable elements (TEs) comprise almost half of primate genomes and their aberrant regulation can result in deleterious effects. In pluripotent stem cells, rapidly-evolving KRAB-ZNF genes target TEs for silencing by H3K9me3. To investigate the evolution of TE silencing, we performed H3K9me3 ChIP-seq experiments in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We identified four million orthologous TEs and found the SVA and ERV families to be marked most frequently by H3K9me3. We found little evidence of inter-species differences in TE silencing, with as many as 82% of putatively silenced TEs marked at similar levels in humans and chimpanzees. TEs that are preferentially silenced in one species are a similar age to those silenced in both species, and are not more likely to be associated with expression divergence of nearby orthologous genes. Our data suggest limited species-specificity of TE silencing across six million years of primate evolution.

Data availability

The following data sets were generated
    1. Ward MC
    (2017) Epigenomic conservation of transposable element silencing
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE96712).
The following previously published data sets were used

Article and author information

Author details

  1. Michelle C Ward

    Department of Human Genetics, University of Chicago, Chicago, United States
    For correspondence
    mcward@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1485-320X
  2. Siming Zhao

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kaixuan Luo

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bryan J Pavlovic

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7751-5315
  5. Mohammad M Karimi

    MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew Stephens

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yoav Gilad

    Department of Human Genetics, University of Chicago, Chicago, United States
    For correspondence
    gilad@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8284-8926

Funding

National Institute of General Medical Sciences (GM077959)

  • Yoav Gilad

EMBO Long-Term Fellowship/European Commission Marie Curie Actions (ALTF 751-2014)

  • Michelle C Ward

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

Reviewing Editor

  1. Patricia J Wittkopp, University of Michigan, United States

Version history

  1. Received: October 28, 2017
  2. Accepted: April 11, 2018
  3. Accepted Manuscript published: April 12, 2018 (version 1)
  4. Version of Record published: May 9, 2018 (version 2)

Copyright

© 2018, Ward 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

  • 5,169
    Page views
  • 398
    Downloads
  • 17
    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. Michelle C Ward
  2. Siming Zhao
  3. Kaixuan Luo
  4. Bryan J Pavlovic
  5. Mohammad M Karimi
  6. Matthew Stephens
  7. Yoav Gilad
(2018)
Silencing of transposable elements may not be a major driver of regulatory evolution in primate iPSCs
eLife 7:e33084.
https://doi.org/10.7554/eLife.33084

Share this article

https://doi.org/10.7554/eLife.33084

Further reading

    1. Cell Biology
    2. Evolutionary Biology
    Jonathan E Phillips, Duojia Pan
    Research Advance

    The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.

    1. Evolutionary Biology
    2. Immunology and Inflammation
    Zachary Paul Billman, Stephen Bela Kovacs ... Edward A Miao
    Research Article

    Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA–D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.