Genetic loci modulating fitness and life span in Caenorhabditis elegans: categorical trait interval mapping in CL2a x 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 x 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 (chi(2)) 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.