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Dopa decarboxylase (Ddc) affects variation in Drosophila longevity

Abstract

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span1, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains2. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin3. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

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Figure 1: Complementation tests to deficiencies and mutations.
Figure 2: Molecular variation in Ddc.
Figure 3: LD in Ddc.
Figure 4: Association of life span with molecular variation in the Ddc gene region.

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Acknowledgements

We thank R. Anholt, C. Langley, J. Leips and J. O'Donnell for comments on the manuscript. This work was supported by grants from the US National Institutes of Health, the Russian Fund of Basic Research and the Russian Academy of Science. This is a publication of the W. M. Keck Center for Behavioral Biology.

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Correspondence to Trudy F C Mackay.

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De Luca, M., Roshina, N., Geiger-Thornsberry, G. et al. Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. Nat Genet 34, 429–433 (2003). https://doi.org/10.1038/ng1218

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