title: 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 span, 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 strains. 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 serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.
authors.affiliation: Department of Genetics, Box 7614, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: De Luca
authors.forename: Nataliya V
authors.initials: NV
authors.lastname: Roshina
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Geiger-Thornsberry
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lyman
authors.forename: Elena G
authors.initials: EG
authors.lastname: Pasyukova
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D004296:Dopa Decarboxylase / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D017344:Genes, Insect; D005816:Genetic Complementation Test; D014644:Genetic Variation; D008136:Longevity / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
chemical_list: D004247:DNA; D004296:Dopa Decarboxylase