Alternative 3' Polyadenylation Responses to Acute Ethanol Exposure Differ Between Drosophila Populations

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Alternative polyadenylation (APA) generates mRNA isoforms with diverse 3' untranslated regions (3' UTRs), impacting gene expression.
• Ethanol serves as an environmental stressor for Drosophila melanogaster, with natural populations exhibiting varied responses.
• The influence of natural genetic variation on ethanol-responsive APA is not well understood.

Purpose of the Study:

• To investigate how natural genetic variation affects ethanol-responsive APA in Drosophila melanogaster.
• To compare APA profiles between cosmopolitan (French) and ancestral range (Zambian) D. melanogaster genotypes upon ethanol exposure.

Main Methods:

• Profiling of 3' end isoforms in response to acute ethanol exposure across six D. melanogaster genotypes (three French, three Zambian).
• Identification and analysis of significant alternative polyadenylation (APA) events.
• Comparative analysis of ethanol-induced APA events between populations and genotypes.

Main Results:

• Numerous significant APA events were identified across all genotypes.
• Ethanol-induced APA was widespread but exhibited significant genotype and population-specific patterns.
• French genotypes showed a bias towards 3' UTR shortening (proximal shifts), while Zambian genotypes favored 3' UTR lengthening (distal shifts).
• Most ethanol-responsive APA events were population-specific, with few conserved directional changes.
• Inter-poly(A) site distance did not predict response direction, but spacing magnitude influenced remodeling.

Conclusions:

• Ethanol-responsive 3' end regulation is genetically contingent and flexible.
• Population-specific APA remodeling is a potential molecular mechanism underlying adaptation to environmental stressors.
• Understanding APA variation is crucial for comprehending adaptive responses to environmental challenges.