Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

  1. Ambuj Upadhyay
  2. Nathan R Feltman
  3. Adam Sychla
  4. Anna Janzen
  5. Siba R Das
  6. Maciej Maselko
  7. Michael Smanski  Is a corresponding author
  1. University of Minnesota, United States
  2. Macquarie University, Australia

Abstract

Engineered Genetic Incompatibility (EGI) is a method to create species-like barriers to sexual reproduction. It has applications in pest control that mimic Sterile Insect Technique when only EGI males are released. This can be facilitated by introducing conditional female-lethality to EGI strains to generate a sex-sorting incompatible male system (SSIMS). Here, we demonstrate a proof of concept by combining tetracycline-controlled female lethality constructs with a pyramus-targeting EGI line in the model insect Drosophila melanogaster. We show that both functions (incompatibility and sex-sorting) are robustly maintained in the SSIMS line and that this approach is effective for population suppression in cage experiments. Further we show that SSIMS males remain competitive with wild-type males for reproduction with wild-type females, including at the level of sperm competition.

Data availability

All data is available in the manuscript

Article and author information

Author details

  1. Ambuj Upadhyay

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States
    Competing interests
    Ambuj Upadhyay, Inventor of filed patents (PCT/US2019/059826).
  2. Nathan R Feltman

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, United States
    Competing interests
    Nathan R Feltman, Inventor of filed patents.(PCT/US2019/059826).
  3. Adam Sychla

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, United States
    Competing interests
    No competing interests declared.
  4. Anna Janzen

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, United States
    Competing interests
    No competing interests declared.
  5. Siba R Das

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, United States
    Competing interests
    Siba R Das, Inventor on filed IP, co-founder of Novoclade. (PCT/US2019/059826).
  6. Maciej Maselko

    Macquarie University, Sydney, Australia
    Competing interests
    Maciej Maselko, Inventor of filed IP; co-founder of Novoclade. (PCT/US2019/059826).
  7. Michael Smanski

    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, United States
    For correspondence
    smanski@umn.edu
    Competing interests
    Michael Smanski, Inventor on filed patents and co-founder of Novoclade. (PCT/US2019/059826).
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6029-8326

Funding

Minnesota Invasive Terrestrial Plants and Pests Center, University of Minnesota

  • Michael Smanski

Defense Advanced Research Projects Agency

  • Michael Smanski

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

Ethics

Animal experimentation: Work with invertebrates (e.g. D. melanogaster) is exempt from the University of Minnesota's IACUC research oversight, however all work was approved by UMN's Institutional Biosafety Committee.

Copyright

© 2022, Upadhyay 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

  • 1,940
    views
  • 249
    downloads
  • 17
    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. Ambuj Upadhyay
  2. Nathan R Feltman
  3. Adam Sychla
  4. Anna Janzen
  5. Siba R Das
  6. Maciej Maselko
  7. Michael Smanski
(2022)
Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression
eLife 11:e71230.
https://doi.org/10.7554/eLife.71230

Share this article

https://doi.org/10.7554/eLife.71230

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Omid Gholamalamdari, Tom van Schaik ... Andrew S Belmont
    Research Article

    Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.

    1. Cell Biology
    2. Genetics and Genomics
    Keva Li, Nicholas Tolman ... UK Biobank Eye and Vision Consortium
    Research Article

    A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve = 0.579), they offered marginal prediction improvement in PRS-only-based models (p=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites—lactate (p=8.8E-12), pyruvate (p=1.9E-10), and citrate (p=0.02)—linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (Pinteraction = 0.011). Higher total resilience metabolite levels within the highest PRS quartile corresponded to lower glaucoma prevalence (Odds Ratiohighest vs. lowest total resilience metabolite quartile=0.71, 95% Confidence Interval = 0.64–0.80). As pyruvate is a foundational metabolite linking glycolysis to tricarboxylic acid cycle metabolism and ATP generation, we pursued experimental validation for this putative resilience biomarker in a human-relevant Mus musculus glaucoma model. Dietary pyruvate mitigated elevated intraocular pressure (p=0.002) and optic nerve damage (p<0.0003) in Lmx1bV265D mice. These findings highlight the protective role of pyruvate-related metabolism against glaucoma and suggest potential avenues for therapeutic intervention.