Two novel, tightly linked, and rapidly evolving genes underlie Aedes aegypti mosquito reproductive resilience during drought
- Rockefeller University, United States
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
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Aedes aegypti ovary bulk RNA-seqNCBI Gene Expression Omnibus, GSE193470.
Article and author information
Author details
Krithika Venkataraman
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
- 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
- Preprint posted: March 2, 2022 (view preprint)
- Received: May 22, 2022
- Accepted: January 29, 2023
- Accepted Manuscript published: February 6, 2023 (version 1)
- 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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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
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