Genetic and environmental interactions outweigh mitonuclear coevolution for complex traits in Drosophila

Area of Science:

• Evolutionary Genetics
• Genomics
• Molecular Biology

Background:

• Mitochondrial DNA (mtDNA) variation is crucial for phenotypic evolution due to epistatic interactions with the nuclear genome.
• Understanding the interplay between nuclear and mitochondrial genomes is key to deciphering complex trait evolution.
• Quantifying selection pressures (stabilizing and directional) on complex traits is a central challenge in evolutionary genetics.

Purpose of the Study:

• To quantify the contributions of mitochondrial, nuclear, and environmental factors to complex traits.
• To investigate the role of mitonuclear genotype-by-environment interactions in maintaining genetic variation.
• To assess the impact of within-species versus between-species mitochondrial variation on trait architecture.

Main Methods:

• Utilized a panel of 90 Drosophila mitonuclear genotypes.
• Assessed four metabolically demanding complex traits.
• Exposed flies to rotenone (a mitochondrial Complex I inhibitor) to study genotype-by-environment interactions.

Main Results:

• Observed stronger mitonuclear interaction effects with within-species mitochondrial variation, suggesting stabilizing selection.
• Identified significant genotype x environment (GxE and GxGxE) interactions when flies were cultured on rotenone.
• Demonstrated that both nuclear and mitochondrial genomes, along with environmental factors, contribute to complex traits.

Conclusions:

• Mitonuclear interactions play a significant role in shaping complex traits and maintaining genetic variation.
• Environmental factors, such as rotenone exposure, reveal complex genetic interactions.
• Findings suggest that mitochondrial DNA donors with longer purifying selection histories may be safer for mitochondrial replacement therapies.