Genetic analysis of extended life span in Drosophila melanogaster. II. Replication of the backcross test and molecular characterization of the N14 locus.

Abstract

We are interested in localizing chromosomal regions that extend life span in Drosophila. Using stocks artificially selected for long life by Luckinbill and his colleagues, we have identified marker loci that are highly divergent in allelic frequencies between replicated long-lived lines and controls (Curtsinger et al., 1998). Several of the most divergent loci have been found to be associated with effects on life span in segregating backcross populations. Here we report an independent replication of the backcross test for the N14 marker locus, previously reported to extend male life spans by 12 days. The life span effect successfully replicates in males. N14 accounts for 30% of the total selection response in males. Life span extension occurs by a decrease in age-specific mortality rates at all ages, and is not attributable to modification of the slope of the age-specific mortality curve. The effect in females is small or nonexistent. Sequencing of the N14 locus shows that it is non-coding and not obviously regulatory, suggesting that the phenotypic effect arises from linkage disequilibrium with another locus or loci that directly affect life span. N14 DNA hybridizes to 63F/64A on the left arm of chromosome 3. The location is consistent with previous whole-chromosome substitution studies, and suggests new candidate genes for life span extension in Drosophila, including ras2.