The Lifespan of D. melanogaster Depends on the Function of the Gagr Gene, a Domesticated gag Gene of Drosophila LTR Retrotransposons

Abstract

(1) Background: The Gagr gene in Drosophila melanogaster’s genome originated from the molecular domestication of retrotransposons and retroviruses’ gag gene. In all Drosophila species, the Gagr protein homologs exhibit a conserved structure, indicative of a vital role. Previous studies have suggested a potential link between the Gagr gene function and stress responses. (2) Methods: We compared flies with Gagr gene knockdown in all tissues to control flies in physiological tests and RNA-sequencing experiments. (3) Results: Flies with the Gagr gene knockdown exhibited shorter lifespans compared to control flies. Transcriptome analysis revealed that Gagr knockdown flies showed elevated transcription levels of immune response genes. We used ammonium persulfate, a potent stress inducer, to elicit a stress response. In control flies, ammonium persulfate activated the Toll, JAK/STAT, and JNK/MAPK signaling pathways. In contrast, flies with the Gagr gene knockdown displayed reduced expression of stress response genes. Gene ontology enrichment analysis identified categories of genes upregulated under ammonium persulfate stress in control flies but not in Gagr knockdown flies. These genes are involved in developmental control, morphogenesis, and central nervous system function. (4) Conclusion: Our findings indicate the significance of the Gagr gene in maintaining immune response and homeostasis.