Briefing Document: Radiation-Induced Alternative Splicing in Aedes aegypti MosquitoesSource: Bendzus-Mendoza, H., Rodriguez, A., Debnath, T., Bailey, C. D., Luker, H. A., & Hansen, I. A. (2025). Radiation exposure induces genome-wide alternative splicing events in Aedes aegypti mosquitoes. Scientific Reports, 15, 5885.Date of Publication: Received - 19 June 2024 | Accepted - 14 March 2025 | Published - 24 March 2025Key Themes and Important Ideas/Facts:This study investigates the impact of ionizing radiation on alternative splicing events (ASEs) in male Aedes aegypti mosquitoes, a crucial aspect for improving the sterile insect technique (SIT). The researchers compared RNA sequencing data from male mosquitoes irradiated with a standard dose of 50 Grey (Gy) of X-rays to that of un-irradiated control mosquitoes. Their findings reveal that radiation exposure induces significant changes in alternative splicing patterns across the mosquito genome, affecting genes involved in key biological processes.1. Background and Motivation:Aedes aegypti is a major vector for several deadly diseases, posing a significant public health threat. Controlling their populations is crucial."Aedes aegypti, the yellow fever mosquito, is the primary vector of several deadly diseases, including yellow fever, dengue fever, chikungunya, and Zika[1]. These insects are a major public health threat in many parts of the world, especially in tropical and subtropical regions[2,3]."SIT, which involves releasing sterile males to mate with wild females, is an environmentally friendly method for controlling pest populations."An alternative method for controlling Ae. aegypti populations is the sterile insect technique (SIT).""SIT has been proven safe, effective, and environmentally friendly since it does not involve the use of pesticides. It is species-specific and does not make use of genetically modified organisms[10]."Ionizing radiation is the preferred method for sterilizing male insects in SIT programs, typically using doses between 5 and 300 Gy depending on the species. The optimal dose for Ae. aegypti is 50 Gy."The use of ionizing radiation to sterilize male insects is the method of choice in many SIT programs[11].""The optimal radiation dosage for sterilizing male Ae. aegypti has been previously determined to be 50 Gy[16]."A significant challenge with SIT is that while 50 Gy sterilizes males, it also reduces their fitness and lifespan, hindering their ability to compete with wild males."While irradiating mosquitoes with 50 Gy causes complete sterility, it still reduces male fitness and lifespan[17]. This is a problem because sterile males must successfully compete with wild males for SIT to be effective."Previous research by the same group identified significant changes in gene expression (upregulation of DNA repair genes) in irradiated Ae. aegypti. This study focuses on the impact of radiation on alternative splicing."To better understand the impact of radiation exposure on mosquitoes, we previously investigated changes in the transcriptome of irradiated male Ae. aegypti. We found dramatic changes in the transcriptome, specifically a robust up-regulation of the transcription of DNA repair genes..."2. Key Findings on Alternative Splicing Events (ASEs):Radiation exposure significantly induced alternative splicing events in male Ae. aegypti."The results of our analysis of our dataset confirmed our hypothesis that radiation-exposure triggers specific and significant ASEs in mosquitoes."The study identified 289 significantly differentially alternatively spliced events (FDR < 0.05 and |Δ PSI| > 0.1) in 181 unique genes after irradiation."In total, we detected 15,016 ASEs among the transcriptomes of irradiated and non-irradiated mosquitoes... 289 of these ASEs were significantly differentially alternatively spliced between both groups... with 181 unique genes undergoing ASEs..."Five main types of ASEs were observed: alternative 3’ splice site (A3SS), alternative 5’ splice site (A5SS), mutually exclusive exon (MXE), retained intron (RI), and skipped exon (SE)."Specifically, 88 events were classified as alternative 3’ splice site events (A3SS), 104 as alternative 5’ splice site events (A5SS), 17 as mutually exclusive exon events (MXE), 12 as retained intron (RI) events, and 68 as skipped exon events (SE)..."A3SS, A5SS, and SE were the most prevalent types of ASEs induced by radiation. RI was the least common."Of these five, A3SS, A5SS, and SE are by far the most prevalent after irradiation treatment... In support of this notion, we found that RI is indeed the rarest type of ASE in our Ae. aegypti dataset."These radiation-induced ASEs occurred genome-wide, affecting genes on all three chromosomes of Ae. aegypti."The genes that undergo significant ASEs after irradiation were mapped to the three chromosomes of Ae. aegypti... We found that all five ASEs occurred genome wide."3. Functional Analysis of Alternatively Spliced Genes (ASGs):...
