Dopa decarboxylase (Ddc) affects variation in Drosophila longevity

Area of Science:

• Genetics
• Evolutionary Biology
• Gerontology

Background:

• Genes affecting metabolism and stress resistance are known to influence lifespan in model organisms.
• However, the specific genes driving lifespan variation in natural populations remain largely unknown.
• Previous work identified quantitative trait loci (QTLs) associated with longevity differences in Drosophila melanogaster.

Purpose of the Study:

• To identify genes responsible for natural variation in lifespan within a natural population.
• To investigate the role of the Dopa decarboxylase (Ddc) gene in determining individual longevity.

Main Methods:

• Fine-mapping of a longevity QTL in the 36E;38B cytogenetic interval of Drosophila melanogaster chromosome 2.
• Complementation tests with known mutations to assess Ddc as a positional candidate gene.
• Linkage disequilibrium (LD) mapping using 173 alleles from a natural population to analyze molecular polymorphisms within Ddc.

Main Results:

• The longevity QTL contains multiple linked QTLs, including the Dopa decarboxylase (Ddc) locus.
• Three common molecular polymorphisms within the Ddc gene explain 15.5% of the genetic variance in lifespan.
• These polymorphisms are in strong linkage disequilibrium, and their haplotype effects suggest balancing selection maintenance.

Conclusions:

• Variation in the Dopa decarboxylase (Ddc) gene is a significant contributor to natural variation in lifespan.
• Ddc's role in synthesizing dopamine and serotonin implicates bioamine synthesis variation in individual longevity.
• Balancing selection may maintain polymorphisms in Ddc due to their effects on lifespan.