Genetic Loci Modulating Fitness and Life Span in Caenorhabditis elegans: Categorical Trait Interval Mapping in CL2a × Bergerac-BO Recombinant-Inbred Worms

摘要

Quantitative trait loci (QTL) can implicate an unbiased sampling of genes underlying a complex, polygenic phenotype. QTL affecting longevity in Caenorhabditis elegans were mapped using a CL2a × Bergerac-BO recombinant-inbred population. Genotypes were compared at 30 transposon-specific markers for two paired sample sets totaling 171 young controls and 172 longevity-selected worms (the last-surviving 1%) from a synchronously aged population. A third sample set, totaling 161 worms from an independent culture, was analyzed for confirmation of loci. At least six highly significant QTL affecting life span were detected both by single-marker (χ2) analysis and by two interval-mapping procedures—one intended for nonparametric traits and another developed specifically for mapping of categorical traits. These life-span QTL were located on chromosomes I (near the hP4 locus), III (near stP127 ), IV (near stP44 ), V (a cluster of three peaks, near stP192, stP23 , and stP6 ), and X (two distinct peaks, near stP129 and stP2 ). Epistatic effects on longevity were also analyzed by Fisher's exact test, which indicated a significant life-span interaction between markers on chromosomes V ( stP128 ) and III ( stP127 ). Several further interactions were significant in the initial unselected population; two of these, between distal loci on chromosome V, were completely eliminated in the long-lived subset. Allelic longevity effects for two QTL, on chromosomes IV and V, were confirmed in backcrossed congenic lines and were highly significant in two very different environments—growth on solid agar medium and in liquid suspension culture.