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NATURAL VARIATION IN RADIOTOLERANCE IS ASSOCIATED WITH DIFFERENCES IN INNATE IMMUNE ACTIVITY AND S-PHASE
Llewellyn Green1,2, Shahrzad Hajiarbabi1, Erin Kelleher1
1Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
Biorxiv : the Preprint Server for Biology
|May 25, 2026
Summary
Researchers identified natural genetic variation influencing ionizing radiation tolerance in fruit flies. This study highlights new genes involved in cell-cycle regulation and immune function, crucial for understanding radiation sensitivity.
Area of Science:
- Genetics
- Radiation Biology
- Evolutionary Biology
Background:
- Organismal tolerance to ionizing radiation is a key trait impacting human health and technology.
- While DNA damage response (DDR) pathways are known, natural genetic variation in radiotolerance remains underexplored.
- Natural variation can reveal distinct genes and pathways compared to mutant screens due to evolutionary selection.
Purpose of the Study:
- To identify natural genetic variation affecting radiotolerance in *Drosophila melanogaster*.
- To uncover novel genes and pathways contributing to radiation tolerance through natural selection.
Main Methods:
- Generated a genetically diverse multiparental *Drosophila melanogaster* population.
- Exposed larvae to a semi-lethal dose of ionizing radiation.
- Performed extreme quantitative trait loci (QTL) mapping by sequencing survivors and comparing haplotypes to controls.
Main Results:
- Identified a single major effect QTL on the 3rd chromosome centromere associated with radiotolerance.
- The QTL region contains 34 genes, none previously linked to radiation tolerance.
- Forward genetic analysis and RNA-sequencing implicated cell-cycle regulation and innate immune function genes.
Conclusions:
- Natural genetic variation significantly influences ionizing radiation tolerance in *Drosophila melanogaster*.
- Novel genes involved in cell-cycle regulation and innate immunity are critical for radiotolerance.
- This research provides new insights into the genetic architecture of radiation tolerance beyond known DDR pathways.
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