Obesity is a metabolic disorder related to improper control of energy uptake and expenditure, which results in excessive accumulation of body fat. Initial insights into the genetic pathways that regulate energy metabolism have been provided by a discrete number of obesity-related genes that have been identified in mammals. Here, we report the identification of the adipose (adp) gene, the mutation of which causes obesity in Drosophila. Loss of adp activity promotes increased fat storage, which extends the lifespan of mutant flies under starvation conditions. By contrast, adp gain-of-function causes a specific reduction of the fat body in Drosophila. adp encodes an evolutionarily conserved WD40/tetratricopeptide-repeat-domain protein that is likely to represent an intermediate in a novel signalling pathway.

Laboratory strains of Drosophila melanogaster were screened for spatial variations in adult midgut a-amylase (1,4-a-D-glucan glucanohydrolase, EC 3.2.1.1) expression. No strain-specific ifferences were found anteriorly, but three patterns of activity were discerned in the posterior midgut: A, activity throughout most of the region; B. activity in the anterior part of the region; and C, litte or no activity. Alleles of a control gene, map, are responsible for this tissue-specific regulation of activity: e.g., mapA homozygotes produce the A pattern and map C homozygotes the C pattern. The map locus was placed at 2-80: on the genetic map of chromosome 2R, about two crossover units distal to the Amy structural gene region for aamylase. Electrophoretic studies showed that mapA is trans acting in mapA/mapC flies, allowing expression of amylase isozymes coded for by genes on the opposite chromosome. The map gene behaves as a temporal gene that is clearly separable from the tightly linked, duplicated Amy structural genes.Difterential expression of genes in time and space plays an essential role in eukaryotic development. Two general classes of genes are involved: structural genes and genes with regulatory function (14). Among higher eukaryotes, genes with regulatory function may be subdivided into those that map very close to, or are part of, the structural gene (e.g., refs. 5-11) and those that map some distance from the structural gene (e.g., refs. 11-13). We describe here a control gene of the latter type which is trans acting in its effect on the expression of the structural genes for two discrete a-amylases (1,4-a-D-glucan glucanohydrolase, EC 3.2.1.1). This gene affects amylase activity in the posterior midgut of Drosophila melanogaster in a tissue-specific manner. It fulfills the definition of a temporal gene, i.e., one that encodes genetic information for the developmental program (2, 3, 10).We assumed that regulatory variants for enzyme activities not critical to the life of the organism exist among different populations of Drosophila. Furthermore, a search for such variants would be greatly facilitated by the demonstration of changes in activity or distribution of a given enzyme in a particular tissue, rather than in the organism as a whole. Changes of this sort are especially relevant to the genetic analysis of development (14). The amylase system in D. melanogaster is well characterized at the genetic and biochemical levels and is well suited for this type of analysis (15)(16)(17)(18)(19)(20)(21)(22).In D. melanogaster, a-amylase activity is found mainly in the midgut and hemolymph, with smaller amounts in other tissues (17). We studied the genetic control of that activity in the midguts of adult females. During metamorphosis, the adult midgut arises de novo from stem cells located along the basement membrane of the larval midgut, which is histolyzed (23). The adult midgut has three morphologically distinguishable regions: anterior midgut, middle midgut, and posterior midgut. The anterior and poste...

Contrary to earlier statements, meiosis goes to completion in "Linfertilized" eggs of Drosophila melanogaster. Evidence suggests that this is not only characteristic of the strain examined but of the species as a whole and of other Drosophila species as well.

The amylases of D. melanogaster were characterized by several parameters. Starch-iodine and 3,5-dinitrosalicylic acid reduction methods were employed to determine activity. Conditions were defined under which activity, in crude aqueous extracts could be restricted to a-amylase(s) of fly origin. Biochemical properties of the a-amylases from eleven homozygous A m y strains were found to be very similar in temperature stability, pH optimum, substrate specificity and the effects of various activators and inhibitors. All were activated by chloride ions and showed a pH optimum of about 7.4. Relative efficiencies on several substrates were tested: soluble starch, amylopectin, @-limit dextrins, glycogen and amylose. EDTA completely inhibited all extracts, presumably by the removal of calcium required for activation.The specific a-amylase inhibitor from wheat grain also completely inhibited activity, as did reduced glutathione. PCMB had no discernible effects on activity.Eight of the 11 strains tested are known to produce different electrophoretic banding patterns for amylases. The total maximum activty of each strain may also be used to characterize it and, accordingly, three strains with amylases of the same electrophoretic mobility were distinguished by differences in their specific activities. Sexual dimorphism in amylase activity was defined, as well as activity in heterozygotes between strains. Aside from the distinctions between strains already noted, four strains differed in their relative susceptibility to heat and to a-amylase inhibitor.Linkage experiments indicated that the A m y region lies at 77.3 on the genetic map of the second chromosome and tc? the right, but near, section 52F on the salivary chromosome map.The amylases of Drosophila melanogaster have been described previously in terms of the relative activities and electrophoretic mobilities that characterize them in various Amylase ( A m y ) strains of flies (Abe, '58; Kikkawa and Abe, '60; Kikkawa, '60, '64; Doane, '67a; Bahn, '68). Emphasis has been on their genetic control, while little has been published about their biochemical properties. It was necessary to define some of these properties in order to develop a method for the qualitative and quantitative analysis of the isoamylases separated by disc electrophoresis (Doane, '67a,b). Results of the experiments performed for this purpose and data in support of the view that these are a-amylases will be presented here. These and other data substantiate, clarify, or augment earlier observations on the nature and genetic control of amylases in this species. Included are the results of linkage experiments that pertain to the location of the A m y region on both the crossover and J. EXP. ZOOL., 171: 321-342.

No abstract