Guy1, a Y-linked embryonic signal, regulates dosage compensation in Anopheles stephensi by increasing X gene expression

  1. Yumin Qi
  2. Yang Wu
  3. Randy Saunders
  4. Xiaoguang Chen
  5. Chunhong Mao
  6. James Kite Biedler  Is a corresponding author
  7. Zhijian Jake Tu  Is a corresponding author
  1. Virginia Tech, United States
  2. Southern Medical University, China
  3. Virginia Biocomplexity Institute, United States

Abstract

We previously showed that Guy1, a primary signal expressed from the Y chromosome, is a strong candidate for a male-determining factor that confers female-specific lethality in Anopheles stephensi (Criscione et al., 2016). Here we present evidence that Guy1 increases X gene expression in Guy1-transgenic females from two independent lines, providing a mechanism underlying the Guy1-conferred female lethality. The median level gene expression (MGE) of X-linked genes is significantly higher than autosomal genes in Guy1-transgenic females while there is no significant difference in MGE between X and autosomal genes in wild type females. Furthermore, Guy1 significantly up-regulates at least 40% of the 996 genes across the X chromosome in transgenic females. Guy1-conferred female-specific lethality is remarkably stable and completely penetrant. These findings indicate that Guy1 regulates dosage compensation in An. stephensi and components of dosage compensation may be explored to develop novel strategies to control mosquito-borne diseases.

Data availability

Data submitted to SRA, PRJNA503140 : The transcriptome of Guy1-transgenic Anopheles stephensi L1 instar (TaxID: 30069)

The following data sets were generated

Article and author information

Author details

  1. Yumin Qi

    Department of Biochemistry, Virginia Tech, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yang Wu

    Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1207-5566
  3. Randy Saunders

    Department of Biochemistry, Virginia Tech, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaoguang Chen

    Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Chunhong Mao

    Virginia Biocomplexity Institute, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. James Kite Biedler

    Department of Biochemistry, Virginia Tech, Blacksburg, United States
    For correspondence
    jbiedler@vt.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhijian Jake Tu

    Department of Biochemistry, Virginia Tech, Blacksburg, United States
    For correspondence
    jaketu@vt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4227-3819

Funding

National Institutes of Health (AI105575)

  • Zhijian Jake Tu

National Institutes of Health (AI121284)

  • Zhijian Jake Tu

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

Ethics

Animal experimentation: This study was performed in strict 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 (IACUC #16-067) of the Virginia Tech.

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: November 16, 2018
  2. Accepted: March 16, 2019
  3. Accepted Manuscript published: March 19, 2019 (version 1)
  4. Version of Record published: March 29, 2019 (version 2)

Copyright

© 2019, Qi 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

  • 1,166
    Page views
  • 182
    Downloads
  • 11
    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. Yumin Qi
  2. Yang Wu
  3. Randy Saunders
  4. Xiaoguang Chen
  5. Chunhong Mao
  6. James Kite Biedler
  7. Zhijian Jake Tu
(2019)
Guy1, a Y-linked embryonic signal, regulates dosage compensation in Anopheles stephensi by increasing X gene expression
eLife 8:e43570.
https://doi.org/10.7554/eLife.43570

Further reading

    1. Developmental Biology
    2. Evolutionary Biology
    Sílvia Chafino, Panagiotis Giannios ... Xavier Franch-Marro
    Research Article Updated

    During development, the growing organism transits through a series of temporally regulated morphological stages to generate the adult form. In humans, for example, development progresses from childhood through to puberty and then to adulthood, when sexual maturity is attained. Similarly, in holometabolous insects, immature juveniles transit to the adult form through an intermediate pupal stage when larval tissues are eliminated and the imaginal progenitor cells form the adult structures. The identity of the larval, pupal, and adult stages depends on the sequential expression of the transcription factors chinmo, Br-C, and E93. However, how these transcription factors determine temporal identity in developing tissues is poorly understood. Here, we report on the role of the larval specifier chinmo in larval and adult progenitor cells during fly development. Interestingly, chinmo promotes growth in larval and imaginal tissues in a Br-C-independent and -dependent manner, respectively. In addition, we found that the absence of chinmo during metamorphosis is critical for proper adult differentiation. Importantly, we also provide evidence that, in contrast to the well-known role of chinmo as a pro-oncogene, Br-C and E93 act as tumour suppressors. Finally, we reveal that the function of chinmo as a juvenile specifier is conserved in hemimetabolous insects as its homolog has a similar role in Blatella germanica. Taken together, our results suggest that the sequential expression of the transcription factors Chinmo, Br-C and E93 during larva, pupa an adult respectively, coordinate the formation of the different organs that constitute the adult organism.

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Brian Silver, Kevin Gerrish, Erik Tokar
    Research Article

    Cell-free DNA (cfDNA) present in the bloodstream or other bodily fluids holds potential as a non-invasive diagnostic for early disease detection. However, it remains unclear what cfDNA markers might be produced in response to specific tissue-level events. Organoid systems present a tractable and efficient method for screening cfDNA markers. However, research investigating the release of cfDNA from organoids is limited. Here, we present a scalable method for high-throughput screening of cfDNA from cardiac organoids. We demonstrate that cfDNA is recoverable from cardiac organoids, and that cfDNA release is highest early in differentiation. Intriguingly, we observed that the fraction of cell-free mitochondrial DNA appeared to decrease as the organoids developed, suggesting a possible signature of cardiac organoid maturation, or other cardiac growth-related tissue-level events. We also observe alterations in the prevalence of specific genomic regions in cardiac organoid-derived cfDNA at different timepoints during growth. In addition, we identify cfDNA markers that were increased upon addition of cardiotoxic drugs, prior to the onset of tissue demise. Together, these results indicate that cardiac organoids may be a useful system towards the identification of candidate predictive cfDNA markers of cardiac tissue development and demise.