Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan

Abstract

SummaryVariation in longevity in natural populations is attributable to the segregation of multiple interacting loci, whose effects are sensitive to the environment. Although there has been considerable recent progress towards understanding the environmental factors and genetic pathways that regulate lifespan, little is known about the genes causing naturally occurring variation in longevity. Previously, we used deficiency complementation mapping to map two closely linked quantitative trait loci (QTL) causing femalespecific variation in longevity between the Oregon (Ore) and 2b strains of Drosophila melanogaster to 35B9-C3 and 35C3 on the second chromosome. The 35B9-C3 QTL encompasses a 50-kb region including four genes, for one of which, shuttle craft ( stc ), mutations have been generated. The 35C3 QTL localizes to a 200-kb interval with 15 genes, including three genes for which mutations exist ( reduced ( rd ), guftagu ( gft ) and ms(2)35Ci ). Here, we report quantitative complementation tests to mutations at these four positional candidate genes, and show that ms(2)35Ci and stc are novel candidate quantitative trait genes affecting variation in Drosophila longevity. Complementation tests with stc alleles reveal sex-and allele-specific failure to complement, and complementation effects are dependent on the genetic background, indicating considerable epistasis for lifespan. In addition, a homozygous viable stc allele has a sex-specific effect on lifespan. stc encodes an RNA polymerase II transcription factor, and is an attractive candidate gene for the regulation of longevity and variation in longevity, because it is required for motoneuron development and is expressed throughout development. Quantitative genetic analysis of naturally occurring variants with subtle effects on lifespan can identify novel candidate genes and pathways important in the regulation of longevity.

Quantitative Trait Loci for Locomotor Behavior inDrosophila melanogaster

“…Further, consistent with our inference of substantial pleiotropy among the genetic architectures of multiple complex traits, many of the candidate genes affecting variation in locomotor reactivity in these lines have also been implicated as candidate genes affecting other complex traits. Ddc (DeLuca et al 2003), stc (Pasyukova et al 2004), Catsup (Mackay et al 2005), and Lim3 (Mackay et al 2005) are all candidate genes affecting variation in longevity between Ore-R and 2b, and crol is associated with variation in starvation stress resistance between these strains (Harbison et al 2004).…”

Dissecting the genetics of longevity inDrosophila melanogaster

“…47,53,54 While this approach yields much higher resolution, the average deficiency QTL still contains about 50 genes. 6 However, for genes within these QTL for which mutant alleles are available, gene-specific complementation tests have identified seven genes that contribute to longevity variation between Ore and 2b: Catsup, 61 Dopa decarboxylase (Ddc), 54 Diphenol oxidase A2 (Dox-A2), Lim3, 6 ms(2)35Ci, shuttle craft (stc) 62 and tailup (tup). 6 Like many insects, D. melanogaster is capable of expressing a form of diapause, a neuroendocrine-mediated physiological syndrome that results in reproductive quiescence and organismal persistence over long periods of suboptimal conditions.…”

“…For example, lifespan is extended by overexpression of Pcmt at 29°C, but not 25°C; 14 allelic variation at ms(2)35Ci affects male, but not female, longevity. 62 The cross-sex genetic correlation (r GS ) describes the degree to which one locus affects both sexes in a quantitative analysis; r GS values range between -1 (if the same genes affect variation in longevity in males and females, but in opposite directions), 0 (if different genes affect variation in longevity between the sexes) and 1 (if the same genes affect the sexes in the same direction). Estimates of r GS from virgin RILs derived from Ore and 2b strains were approximately 0.2, indicating some, but not complete, consistency between the sexes; when these same lines were mated, and/or reared in stressful conditions, estimates of r GS increased.…”

“…47 For example, QTLs have been identified Epistatic interactions in the expression of longevity have also been demonstrated among lifespan QTL and among marker pairs within inbred lines, some of which show sensitivity to mating status. 6 Individual aging genes identified by mutational 14,[22][23][24]26,27,34,38 and QTL 47,53,[57][58][59]62 analysis also routinely show effects that are differentiated by temperature and/or sex. For example, lifespan is extended by overexpression of Pcmt at 29°C, but not 25°C; 14 allelic variation at ms(2)35Ci affects male, but not female, longevity.…”

Quantitative Trait Loci With Age-Specific Effects on Fecundity in Drosophila melanogaster

“…Verification of the effects of natural genetic variation in candidate genes within QTL regions has also been initiated using association mapping (De Luca et al 2003). While the ''gold standard'' for final confirmation of the effect of sequence variation on phenotypic variation is to functionally characterize the effects of alleles on phenotypes (Mackay 2001;Rong et al 2002;Sun et al 2004), the mapping process has proven to be a promising technique for identifying genes on which to focus our functional genetic efforts (Long et al 1995;Gurganus et al 1999; GeigerThornsberry and Mackay 2004;Moehring and Mackay 2004;Nguyen et al 2004;Palsson and Gibson 2004;Pasyukova et al 2004).In this study we use a population of recombinant inbred lines (RIL) of D. melanogaster to address three issues related to the genetic architecture of age-specific fecundity. First, we map the location of QTL that produce variation in fecundity at two ages (1 week and 4 weeks) and assess their relative influences on fecundity at each age.…”