Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster

Abstract

Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms. Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life. Analyses of Drosophila spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late-age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis. The QTLs had large sex-specific effects on lifespan and agespecific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects. Late ageof-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan.

Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies

“…There are many ways of how to manipulate social environment. One variable that often differs between studies is fly density, ranging from one fly per vial (Nuzhdin et al 1997) to several hundred flies in demography cages (Min et al 2007). Sex differences in demographic parameters may be density-dependent, requiring further examination of our results across a range of different densities.…”

Sex-Specific Effect of Insulin-Dependent Diabetes 4 on Regulation of Diabetes Pathogenesis in the Nonobese Diabetic Mouse

“…This analysis is similar to factorial ANOVA, commonly used in Drosophila genetics to study sex-dependent effects of loci (22)(23)(24)(25)(26)(27)(28)(29)(30). In our case, sex and strain were two discrete covariates.…”

“…7). We used approaches developed in Drosophila complex trait genetics, where multiple sex-specific QTL have been described (22)(23)(24)(25)(26)(27)(28)(29)(30), to look for a sex-specific effect of the Idd loci in the current study. A sex-by-strain interaction effect of T1D incidence was only statistically significant when NOD and NOD.NOR-Idd4 mice were compared ( p ϭ 0.0194), supporting the idea of sex-specific behavior of alleles at the Idd4 locus.…”

Analysis of the effects of inbreeding on lifespan and starvation resistance in Drosophila melanogaster

“…Wang et al (2004) investigated the genetic relationship between longevity and starvation resistance in D. melanogaster and although, in general, the QTL effects were found consistent for sexes and environments a number of QTLs were detected that affected survival only under one of the two conditions (food present or absent). Several QTL mapping studies in D. melanogaster suggest differences in the longevity QTLs due to age (Nuzhdin et al 1997;Curtsinger and Khazaeli 2002;Nuzhdin et al 2005), sex (Nuzhdin et al 1997;Leips andMackay 2000 but see Curtsinger andKhazaeli 2002;Wang et al 2004) and environmental conditions (Leips and Mackay 2000 but see Wang et al 2004).…”