Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

A particularly well-studied evolutionary model is the vinegar fly Drosophila melanogaster, a cosmopolitan insect of ancestral southern-central African origin. Recent work suggests that it expanded out of Africa ∼9,000 years ago, and spread from the Middle East into Europe ∼1,800 years ago. During its global expansion, this human commensal adapted to novel climate zones and habitats. Despite much work on phenotypic differentiation and adaptation on several continents (especially North America and Australia), typically in the context of latitudinal clines, little is known about phenotypic divergence among European populations. Here, we sought to provide a continent-wide study of phenotypic differentiation among European populations of D. melanogaster. In a consortium-wide phenomics effort, we assayed 16 fitness-related traits on a panel of 173 isofemale lines from 9 European populations, with the majority of traits measured by several groups using semi-standardized protocols. For most fitness-related traits, we found significant differentiation among populations on a continental scale. Despite inevitable differences in assay conditions among labs, the reproducibility and hence robustness of our measurements were overall remarkably good. Several fitness components (e.g., viability, development time) exhibited significant latitudinal or longitudinal clines, and populations differed markedly in multivariate trait structure. Notably, populations experiencing higher humidity/rainfall and lower maximum temperature showed higher viability, fertility, starvation resistance, and lifespan at the expense of lower heat-shock survival, suggesting a pattern of local adaptation. Our results indicate that derived populations of this tropical fly have been shaped by pervasive spatially varying multivariate selection and adaptation to different climates on the European continent.

Revealing gene expression patterns is essential for comprehending the genetic control of complex traits like lifespan. Analyzing structural variation in gene regulatory regions within natural populations is a promising approach in functional genetics, allowing us to identify regulatory sites that influence transcription and phenotype in vivo. We describe the structural variability of the 5′ regulatory region of the shuttle craft (stc) gene in the Alexandrov population (Russia) of Drosophila melanogaster, encoding a transcription factor homologous to human NF-X1. We evaluated the association of frequently occurring polymorphisms with fly lifespan from inbred lines sampled in 2010, 2011, and 2014. Two polymorphisms in the stc 5′ regulatory region exhibit strong associations with both lifespan and embryonic stc transcript levels. Their role in expression regulation was evaluated via reporter gene assays conducted in S2 Drosophila cell culture. The ‘C’ allele at one polymorphic site and ‘T’ at the other are associated with increased longevity and decreased embryonic stc transcription, reaffirming the link between gene expression and lifespan we previously established. Furthermore, comparing stc 5′ regulatory region variability across Alexandrov, European and African populations suggests that the macro-geographic distribution of these longevity-associated variants is consistent with a potential role in latitudinal or climatic adaptation.

Bang sensitivity (BS) is a well-characterized seizure-and-paralysis phenotype in Drosophila melanogaster, but its genetic basis remains unexamined in the phylogenetically distant sister species Drosophila funebris. Here, we identify a naturally occurring BS strain in D. funebris from a wild population near Lake Valday, characterized by acute mechanical shock-induced seizures and paralysis, and examine its molecular-genetic and lipidomic basis. Comparative transcriptomics identified 241 differentially expressed genes (FDR-adjusted p < 0.05), with “fatty acid metabolic process” as the most enriched GO term. Notably, within this pathway, the peroxisomal acyl-CoA oxidase gene Acox57D-d showed the most significant downregulation (log₂FC = −4.21, p_adj = 4.1 × 10⁻¹¹⁰), validated by head-specific RT-qPCR. Untargeted lipidomics of BS heads (LC-Q-TOF-MS) revealed 145 altered lipid species, dominated by oxygenated triacylglycerol accumulation, cardiolipin/phosphatidylethanolamine depletion, and a divergent shift—depletion of DG 29:0 and accumulation of DG 47:4, reflecting impaired peroxisomal β-oxidation and potential mitochondrial and Na⁺/K⁺-ATPase dysfunction. These findings nominate Acox57D-d as a leading candidate gene associated with the phenotype and molecular signature of the studied BS line and establish this natural BS strain as a potentially useful model for investigating the relationship between peroxisomal lipid metabolism, neuronal excitability, and insect thanatosis.