Abstract

Female Aedes aegypti mosquitoes impose a severe global public health burden as vectors of multiple viral pathogens. Under optimal environmental conditions, Aedes aegypti females have access to human hosts that provide blood proteins for egg development, conspecific males that provide sperm for fertilization, and freshwater that serves as an egg-laying substrate suitable for offspring survival. As global temperatures rise, Aedes aegypti females are faced with climate challenges like intense droughts and intermittent precipitation, which create unpredictable, suboptimal conditions for egg-laying. Here we show that under drought-like conditions simulated in the laboratory, females retain mature eggs in their ovaries for extended periods, while maintaining the viability of these eggs until they can be laid in freshwater. Using transcriptomic and proteomic profiling of Aedes aegypti ovaries, we identify two previously uncharacterized genes named tweedledee and tweedledum, each encoding a small, secreted protein that both show ovary-enriched, temporally-restricted expression during egg retention. These genes are mosquito-specific, linked within a syntenic locus, and rapidly evolving under positive selection, raising the possibility that they serve an adaptive function. CRISPR-Cas9 deletion of both tweedledee and tweedledum demonstrates that they are specifically required for extended retention of viable eggs. These results highlight an elegant example of taxon-restricted genes at the heart of an important adaptation that equips Aedes aegypti females with 'insurance' to flexibly extend their reproductive schedule without losing reproductive capacity, thus allowing this species to exploit unpredictable habitats in a changing world.

Data availability

RNA-sequencing data have been deposited in GEO under accession code GSE193470.The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD030925. Ovary sample raw files begin with the code "MS205850LUM". Hemolymph sample raw files begin with the code "MS195106LUM".All raw data included in the figures are available at Zenodo: https://doi.org/10.5281/zenodo.5945525

The following data sets were generated

Article and author information

Author details

  1. Krithika Venkataraman

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    For correspondence
    krithika.venkataraman@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2067-2387
  2. Nadav Shai

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Priyanka Lakhiani

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sarah Zylka

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7311-2981
  5. Jieqing Zhao

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Margaret Herre

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Joshua Zeng

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4694-3309
  8. Lauren A Neal

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Henrik Molina

    Proteomics Resource Center, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8950-4990
  10. Li Zhao

    Laboratory of Evolutionary Genetics and Genomics, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6776-1996
  11. Leslie B Vosshall

    Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, United States
    For correspondence
    leslie@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6060-8099

Funding

Boehringer Ingelheim Fonds (BIF PhD Fellowship)

  • Krithika Venkataraman

Sohn Conferences Foundation

  • Henrik Molina

Monique Weill-Caulier Career Scientist Award

  • Li Zhao

Robertson Foundation

  • Li Zhao

Howard Hughes Medical Institute

  • Leslie B Vosshall

Kavli Foundation (KNSI Pre-doctoral fellowship)

  • Margaret Herre

National Institutes of Health (F30DC017658)

  • Margaret Herre

European Molecular Biology Organization (EMBO ALTF 286-2019)

  • Nadav Shai

National Institutes of Health (MIRA R35GM133780)

  • Li Zhao

Rita Allen Foundation (Rita Allen Scholar)

  • Li Zhao

Vallee Foundation (VS-2020-35)

  • Li Zhao

National Institutes of Health (NRSA Training Grant #GM066699)

  • Lauren A Neal

Leona M. and Harry B. Helmsley Charitable Trust

  • Henrik Molina

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

Reviewing Editor

  1. Daniel R Matute, University of North Carolina, Chapel Hill, United States

Ethics

Animal experimentation: Blood-feeding using live mice was approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 17018).

Human subjects: Behavioral experiments and blood-feeding using live hosts were approved and monitored by The Rockefeller University Institutional Review Board (IRB protocol LV-0652). All human subjects gave their written informed consent to participate in this study.

Version history

  1. Preprint posted: March 2, 2022 (view preprint)
  2. Received: May 22, 2022
  3. Accepted: January 29, 2023
  4. Accepted Manuscript published: February 6, 2023 (version 1)
  5. Version of Record published: April 5, 2023 (version 2)

Copyright

© 2023, Venkataraman 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.

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  1. Krithika Venkataraman
  2. Nadav Shai
  3. Priyanka Lakhiani
  4. Sarah Zylka
  5. Jieqing Zhao
  6. Margaret Herre
  7. Joshua Zeng
  8. Lauren A Neal
  9. Henrik Molina
  10. Li Zhao
  11. Leslie B Vosshall
(2023)
Two novel, tightly linked, and rapidly evolving genes underlie Aedes aegypti mosquito reproductive resilience during drought
eLife 12:e80489.
https://doi.org/10.7554/eLife.80489

Share this article

https://doi.org/10.7554/eLife.80489

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