Correlated responses in basal immune function in response to selection for fast development in Drosophila melanogaster.

Often, immunity is invoked in the context of infection, disease and injury. However, an ever alert and robust immune system is essential for maintaining good health, but resource investment into immunity needs to be traded off against allocation to other functions. In this study, we study the consequences of such a trade-off with growth by ascertaining various components of baseline innate immunity in two types of Drosophila melanogaster populations selected for fast development, in combination with either a long effective lifespan (FLJs) or a short effective lifespan (FEJs). We found that distinct immunological parameters were constitutively elevated in both, FLJs and FEJs compared to their ancestral control (JB) populations, and these constitutive elevated immunological parameters were associated with reduced insulin signalling and comparable total gut microbiota. Our results bring into focus the inter-relationship between egg to adult development time, ecdysone levels, larval gut microbiota, insulin signalling, adult reproductive longevity and immune function. We discuss how changes in selection pressures operating on life-history traits can modulate different components of immune system.

Heightened immune surveillance in Drosophila melanogaster populations selected for faster development and extended longevity.

Maximization of life-history traits is under constraints due to both, limitations of resource acquisition and the restricted pathways of resource allocation. Drosophila melanogaster has served as an excellent model organism to not only unravel various trade-offs among life history traits but also numerous aspects of host immune response. Drosophila larvae are semi-aquatic that live, feed and excrete inside the food source-often over-ripe fruits and vegetables that are rich in both commensal and pathogenic microbiota that can impact the larval survival. In this study, we have used six populations of D. melanogaster, three of which are selected for faster pre-adult development and extended adult longevity, and their three ancestral controls, to explore the impact of selection on the basal immune activity in the larval stage. The larvae from selected populations had nearly significantly upregulated plasmatocyte density, significantly higher percent phagocytosis, phagocytic index and higher transcript levels of Tep3, eater and NimC1. Selected populations also had significantly upregulated crystal cell number along with higher transcript of PPO2. Out of seven tested AMPs level, Drosomycin was significantly upregulated in selected populations while Drosocin was significantly higher in control populations. ROS levels were comparable in the selected and control populations. Our results strongly suggest that enhanced basal immune activity during larval stage manages the faster development and could be responsible for comparable larval survival of selected and control populations.

Management of altered metabolic activity in Drosophila model of Huntington's disease by curcumin.

Huntington's disease (HD) is a devastating polyglutamine disorder characterized by extensive neurodegeneration and metabolic abnormalities at systemic, cellular and intracellular levels. Metabolic alterations in HD manifest as abnormal body weight, dysregulated biomolecule levels, impaired adipocyte functions, and defective energy state which exacerbate disease progression and pose acute threat to the health of challenged individuals in form of insulin resistance, cardiovascular disease, and energy crisis. To colossally mitigate disease symptoms, we tested the efficacy of curcumin in Drosophila model of HD. Curcumin is the bioactive component of turmeric (Curcuma longa Linn), well-known for its ability to modulate metabolic activities. We found that curcumin effectively managed abnormal body weight, dysregulated lipid content, and carbohydrate level in HD flies. In addition, curcumin administration lowered elevated reactive-oxygen-species levels in adult adipose tissue of diseased flies, and improved survival and locomotor function in HD flies at advanced disease stage. Altogether, these findings clearly suggest that curcumin efficiently attenuates metabolic derangements in HD flies and can prove beneficial in alleviating the complexities associated with HD.

Fitness consequences of biochemical adaptation in Drosophila melanogaster populations under simultaneous selection for faster pre-adult development and extended lifespan.

In holometabolous insects like Drosophila melanogaster, critical size is an important time point during larval life, for irreversible commitment to metamorphosis. Here, we studied the impact of restricted growth duration in terms of selection for faster pre-adult development in Drosophila melanogaster populations which resulted in the evolution of reduced critical size on adult life history traits. Selection for faster pre-adult development resulted in biochemical adaptation in larval physiology with no compromise in major biomolecules at critical size time point. The flies from the selected populations seem to not only commit to metamorphosis on the attainment of critical size but also seem to channelize resources to reproduction as indicated by similar life-time fecundity of CS and NS flies from selected populations, while the Control CS flies significantly lower life-time fecundity compared to Control NS flies. The flies from selected populations seem to achieve longevity comparable to control flies despite being significantly smaller in size-thus resource constrained due to faster pre-adult development.

Evolution of reduced minimum critical size as a response to selection for rapid pre-adult development in Drosophila melanogaster.

Adult body size in holometabolus insects is directly proportional to the time spent during the larval period. The larval duration can be divided into two parts: (i) pre-critical duration-time required to attain a critical size/critical weight that would result in successful completion of development and metamorphosis even under non-availability of nutrition beyond the time of attainment of critical size, and (ii) post-critical duration-the time duration from the attainment of critical size till pupation. It is of interest to decipher the relative contribution of the two larval growth phases (from the hatching of the egg to the attainment of critical size, and from the attainment of critical size to pupation) to the final adult size. Many studies using Drosophila melanogaster have shown that selecting populations for faster development results in the emergence of small adults. Some of these studies have indirectly reported the evolution of smaller critical size. Using two kinds of D. melanogaster populations, one of which is selected for faster/accelerated pre-adult development and the other their ancestral control, we demonstrate that the final adult size is determined by the time spent as larvae post the attainment of critical size despite having increased growth rate during the second larval instar. Our populations under selection for faster pre-adult development are exhibiting adaptive bailout due to intrinsic food limitation as against extrinsic food limitation in the yellow dung fly.

Wing patterning in faster developing Drosophila is associated with high ecdysone titer and wingless expression.

'Developmental robustness' is the ability of biological systems to maintain a stable phenotype despite genetic, environmental or physiological perturbations. In holometabolous insects, accurate patterning and development is guaranteed by alignment of final gene expression patterns in tissues at specific developmental stage such as molting and pupariation, irrespective of individual rate of development. In the present study, we used faster developing Drosophila melanogaster populations that show reduction of ~22% in egg to adult development time. Flies from the faster developing population exhibit phenotype constancy, although significantly small in size. The reduction in development time in faster developing flies is possibly due to coordination between higher ecdysteroid release and higher expression of developmental genes. The two together might be ensuring appropriate pattern formation and early exit at each development stage in the populations selected for faster pre-adult development compared to their ancestral controls. We report that apart from plasticity in the rate of pattern progression, alteration in the level of gene expression may be responsible for pattern integrity even under reduced development time.

Comparative Genomic Analysis Reveals Habitat-Specific Genes and Regulatory Hubs within the Genus Novosphingobium.

Species belonging to the genus Novosphingobium are found in many different habitats and have been identified as metabolically versatile. Through comparative genomic analysis, we identified habitat-specific genes and regulatory hubs that could determine habitat selection for Novosphingobium spp. Genomes from 27 Novosphingobium strains isolated from diverse habitats such as rhizosphere soil, plant surfaces, heavily contaminated soils, and marine and freshwater environments were analyzed. Genome size and coding potential were widely variable, differing significantly between habitats. Phylogenetic relationships between strains were less likely to describe functional genotype similarity than the habitat from which they were isolated. In this study, strains (19 out of 27) with a recorded habitat of isolation, and at least 3 representative strains per habitat, comprised four ecological groups-rhizosphere, contaminated soil, marine, and freshwater. Sulfur acquisition and metabolism were the only core genomic traits to differ significantly in proportion between these ecological groups; for example, alkane sulfonate (ssuABCD) assimilation was found exclusively in all of the rhizospheric isolates. When we examined osmolytic regulation in Novosphingobium spp. through ectoine biosynthesis, which was assumed to be marine habitat specific, we found that it was also present in isolates from contaminated soil, suggesting its relevance beyond the marine system. Novosphingobium strains were also found to harbor a wide variety of mono- and dioxygenases, responsible for the metabolism of several aromatic compounds, suggesting their potential to act as degraders of a variety of xenobiotic compounds. Protein-protein interaction analysis revealed ß-barrel outer membrane proteins as habitat-specific hubs in each of the four habitats-freshwater (Saro_1868), marine water (PP1Y_AT17644), rhizosphere (PMI02_00367), and soil (V474_17210). These outer membrane proteins could play a key role in habitat demarcation and extend our understanding of the metabolic versatility of the Novosphingobium species. IMPORTANCE This study highlights the significant role of a microorganism's genetic repertoire in structuring the similarity between Novosphingobium strains. The results suggest that the phylogenetic relationships were mostly influenced by metabolic trait enrichment, which is possibly governed by the microenvironment of each microbe's respective niche. Using core genome analysis, the enrichment of a certain set of genes specific to a particular habitat was determined, which provided insights on the influence of habitat on the distribution of metabolic traits in Novosphingobium strains. We also identified habitat-specific protein hubs, which suggested delineation of Novosphingobium strains based on their habitat. Examining the available genomes of ecologically diverse bacterial species and analyzing the habitat-specific genes are useful for understanding the distribution and evolution of functional and phylogenetic diversity in the genus Novosphingobium.

Altered lipid metabolism in Drosophila model of Huntington's disease.

Huntington's disease (HD) is late-onset, progressive neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt) protein. In HD patients, energy-related manifestations such as modulation of weight during entire course of disease with energy deficit at terminal stage have been reported, however, underlying reason remains elusive till date. Lipids, carbohydrate and protein constitute a predominant fraction of body's energy reservoir and perturbation in their homeostasis may influence weight. To discern role of these energy molecules in weight alteration, we quantified them in an in vivo transgenic Drosophila model of HD. We document that diseased flies exhibit change in weight due to an altered lipid metabolism, as evident from considerably high lipid levels at the time of disease onset followed by a pathologic decline at end-stage. An alteration in intracellular lipid droplet size suggested altered cellular lipid turnover. Furthermore, diseased flies displayed substantial changes in carbohydrate and protein content. Interestingly, alteration in weight and lipid levels are independent of the feeding pattern in diseased condition and exhibit weak correlation with insulin-like peptide or adipokinetic hormone producing cells. We propose that therapeutic intervention aimed at restoring lipid levels and associated metabolic pathways may improve longevity and quality of patient's life.

Gender based disruptive selection maintains body size polymorphism in Drosophila melanogaster.

Darwinian fitness in holometabolous insects like the fruit fly Drosophila melanogaster is reported to be positively correlated with body size. If large individuals in a population have higher fitness, then one would expect directional selection to operate leading to uniformly large individuals. However, size polymorphism persists in nature and needs further probing. We assessed the effect of body size on some of the fitness and fitness-related traits in replicate populations of genotypically large, genotypically small and phenotypically small D. melanogaster flies. In this study, the time taken to attain reproductive maturity and copulation duration were independent of fly size. Fecundity and longevity of large females were significantly higher when they partnered genotypically small males than when they were with genotypically larger or phenotypically small males. The increased female longevity when in association with genotypically small males was not due to selective early death of males that would release the female partner from presumed cost of persistent courtship. On the contrary, the genotypically as well as phenotypically small males had significantly higher longevity than large males. The virility of the genotypically small males was not significantly different from that of genotypically large males. Our results clearly show that selection on body size operates in the opposite direction (disruptive selection) for the two genders, thus explaining the persistence of size polymorphisms in the holometabolous insect, Drosophila melanogaster.

Aloe vera or resveratrol supplementation in larval diet delays adult aging in the fruit fly, Drosophila melanogaster.

Longevity extension in Drosophila melanogaster by feeding diet supplemented with chemicals throughout adulthood can cause harmful side effects. We tested the effect of larval diet supplementation with five different concentrations of resveratrol and one concentration of Aloe vera extract on the adult longevity of short-lived D melanogaster populations. Resveratrol and A vera extract supplementation of larval diet extended adult longevity in both the male and female flies without reducing fecundity but by efficient reactive oxygen species scavenging through increased antioxidant enzymes activity and better neuroprotection as indicated by increased locomotor activity in adult males.