fruitless mutant male mosquitoes gain attraction to human odor
- The Rockefeller University, United States
Abstract
The Aedes aegypti mosquito shows extreme sexual dimorphism in feeding. Only females are attracted to and obtain a blood-meal from humans, which they use to stimulate egg production. The fruitless gene is sex-specifically spliced and encodes a BTB zinc-finger transcription factor proposed to be a master regulator of male courtship and mating behavior across insects. We generated fruitless mutant mosquitoes and showed that males failed to mate, confirming the ancestral function of this gene in male sexual behavior. Remarkably, fruitless males also gain strong attraction to a live human host, a behavior that wild-type males never display, suggesting that male mosquitoes possess the central or peripheral neural circuits required to host-seek and that removing fruitless reveals this latent behavior in males. Our results highlight an unexpected repurposing of a master regulator of male-specific sexual behavior to control one module of female-specific blood-feeding behavior in a deadly vector of infectious diseases.
Data availability
All raw data are provided in Data File 1. Plasmids are available at Addgene (#141099, #141100). RNA-seq data are available in the Short Read Archive at Genbank (Bioproject: PRJNA612100). Details of Quattroport fabrication and operation are available at Github: https://github.com/VosshallLab/Basrur_Vosshall2020
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Sex-specific mosquito brain transcriptomesNCBI SRA Bioproject: PRJNA612100.
Article and author information
Author details
Maria Elena De Obaldia
Ricarda K von Heynitz
Funding
Howard Hughes Medical Institute (Vosshall-Investigator)
- Leslie B Vosshall
National Center for Advancing Translational Sciences (UL1 TR000043)
- Leslie B Vosshall
Harvey L. Karp Discovery Award (postdoctoral fellowship)
- Maria Elena De Obaldia
- Takeshi Morita
Japan Society for Promotion of Science (JSPS Overseas Research Fellowship)
- Takeshi Morita
Helen Hay Whitney Foundation (HHW Fellowship)
- Maria Elena De Obaldia
National Center for Advancing Translational Sciences (UL1 TR001866)
- Maria Elena De Obaldia
National Institute on Deafness and Other Communication Disorders (F30DC017658)
- Margaret Herre
National Institute of General Medical Sciences (T32GM007739)
- Margaret Herre
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Blood-feeding procedures with live mice were approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 17018) .
Human subjects: Blood-feeding procedures and behavioral experiments with human volunteers were approved and monitored by The Rockefeller University Institutional Review Board (IRB protocol LV-0652). Human subjects gave their written informed consent to participate.
Copyright
© 2020, Basrur 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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fruitless mutant male mosquitoes gain attraction to human odor
eLife 9:e63982.
https://doi.org/10.7554/eLife.63982
Further reading
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- Epidemiology and Global Health
- Genetics and Genomics
Background:
Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.
Methods:
We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).
Results:
Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (–0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (–0.043±0.013 kg, p=0.0011) in the combined cohorts.
Conclusions:
This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
Funding:
This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.
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- Cancer Biology
- Genetics and Genomics
It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy.
