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The Developmental Origins of Health and Disease hypothesis predicts that early-life environmental exposures can be detrimental to later-life health and that mismatch between the pre- and post-natal environment may contribute to the growing non-communicable disease epidemic. Within this is an increasingly recognized role for epigenetic mechanisms; f...
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Context 1
... data were exported and QC-checked using Nanostring's nSolver data analysis tool (www.nanostring.com). Per the Nanostring CodeSet design criteria, 25 candidate genes for validation were chosen, including two housekeeping genes incorporated (Mnf and Rpl32, Table 2). Raw data were normal- ized to the geometric mean of both the positive controls (included in the hybridisation steps) and the nominated house- keeping genes. ...
Similar publications
The sequenced genomes of the Drosophila phylogeny are a central resource for comparative work supporting the understanding of the Drosophila melanogaster non-mammalian model system. These have also facilitated evolutionary studies on the selected and random differences that distinguish the thousands of extant species of Drosophila . However, full u...
Sex differences in dioecious animals are pervasive and result from gene expression differences. Elevated sexual selection has been predicted to increase the number and expression of male-biased genes, and experimentally imposing monogamy on Drosophila melanogaster has led to a relative feminisation of the transcriptome. Here, we test this hypothesi...
Citations
... Larvae reared on yeast-poor substrates exhibit reduced immunity, have a diminished ability to adapt to unfavorable conditions, and often fail to complete development [27,[29][30][31] . On the other hand, yeast-poor diets can enhance cold tolerance [33] and increase the longevity of D. melanogaster [34,35] . The yeast content in the substrate can have opposing effects on longevity, fecundity, and mating frequency of fly females and males [36] . ...
Aim: Microbiomes influence the physiology and behavior of multicellular organisms and contribute to their adaptation to changing environmental conditions. However, yeast and bacterial microbiota have usually been studied separately; therefore, the interaction between bacterial and yeast communities in the gut of Drosophila melanogaster (D. melanogaster ) is often overlooked. In this study, we investigate the correlation between bacterial and yeast communities in the gut of D. melanogaster .
Methods: We studied the shifts in the joint microbiome of Drosophila melanogaster , encompassing both yeasts and bacteria, during adaptation to substrate with varying salt concentrations (0%, 2%, 4%, and 7%) using plating for both yeasts and bacteria and NGS-sequencing of variable 16S rRNA gene regions for bacteria.
Results: The microbiome of flies and their substrates was gradually altered at moderate NaCl concentrations (2% and 4% compared with the 0% control) and completely transformed at high salt concentrations (7%). The relative abundance of Acetobacter , potentially beneficial to D. melanogaster , decreased as NaCl concentration increased, whereas the relative abundance of the more halotolerant lactobacilli first increased, peaking at 4% NaCl, and then declined dramatically at 7%. At this salinity level, potentially pathogenic bacteria of the genera Leuconostoc and Providencia were dominant. The yeast microbiome of D. melanogaster also undergoes significant changes with an increase in salt concentration in the substrate. The total yeast abundance undergoes nonlinear changes: it is lowest at 0% salt concentration and highest at 2%-4%. At a 7% concentration, the yeast abundance in flies and their substrate is lower than at 2%-4% but significantly higher than at 0%.
Conclusions: The abundance and diversity of bacteria that are potentially beneficial to the flies decreased, while the proportion of potential pathogens, Leuconostoc and Providencia , increased with an increase in salt concentration in the substrate. In samples with a relatively high abundance and/or diversity of yeasts, the corresponding indicators for bacteria were often lowered, and vice versa . This may be due to the greater halotolerance of yeasts compared to bacteria and may also indicate antagonism between these groups of microorganisms.
... Together, these studies suggest that multigenerational maternal age affects may be a part of Drosophilid life histories. Few studies involving parental condition measure changes over three generations -extending beyond direct maternal effects (but see Mondotte et al., 2020 for an effect of immune priming in Drosophila), although there exists robust evidence of multigenerational effects of maternal condition including obesity (Brookhart and Duncan, 2016), heavy metal exposure (Yang et al., 2020), age (Bloch Qazi et al., 2017;Layton et al., 2019), and nutrition (Osborne and Dearden, 2017). Maternal age effects extending across generations can contribute to phenotypic variation within populations. ...
Increasing maternal age is commonly accompanied by decreased fitness in offspring. In Drosophila melanogaster, maternal senescence negatively affects multiple facets of offspring phenotype and fitness. These maternal effects are particularly large on embryonic viability. Identifying which embryonic stages are disrupted can indicate mechanisms of maternal effect senescence. Some maternal effects can also carry-over to subsequent generations. We examined potential multi- and transgenerational effects maternal senescence on embryonic development in two laboratory strains of D. melanogaster. We categorized the developmental stages of embryos from every combination of old and young mother, grandmother and great grandmother. We then modelled embryonic survival across the stages and compared these models among the multigenerational maternal age groups in order to identify which developmental processes were most sensitive to the effects of maternal effect senescence. Maternal effect senescence has negative multigenerational effects on multiple embryonic stages, indicating that maternal provisioning and, possibly epigenetics, but not mutation accumulation, contribute to decreased offspring survival. This study shows the large, early and multi-faceted nature of maternal effects senescence in an insect population.
... The transcriptomic changes observed in offspring that were maintained on a mismatched diet (LPHC) were inherited at moderate levels by F1 and F2 but not by F3 offspring, when they reverted back to F0 levels. These observed changes showed that altered nutrition can have multigenerational effects on the transcriptome [48]. The second study also used fruit flies with the goal of exploring how organisms cope with sudden, unfamiliar environmental challenges, such as toxic stress, and examined resulting transgenerational effects. ...
The credibility of the Weismann barrier has come into question. Several studies in various animal systems, from mice to worms, have shown that novel environmental stimuli can generate an altered developmental or behavioral trait that can be transmitted to offspring of the following generation. Recently, insects have become ideal models to study the inheritance of acquired traits. This is because insects can be reared in high numbers at low cost, they have short generation times and produce abundant offspring. Numerous studies have shown that an insect can modify its phenotype in response to a novel stimulus to aid its survival, and also that this modified phenotypic trait can be inherited by its offspring. Epigenetic mechanisms are likely at play but, most studies do not address the mechanisms that underlie the inheritance of acquired traits in insects. Here we first review general epigenetic mechanisms such as DNA methylation, histone acetylation and small noncoding RNAs that have been implicated in the transmission of acquired traits in animals, then we focus on the few insect studies in which these mechanisms have been investigated.
... Other environmental factors were shown to affect chromatin regulation. For example, varying the level of proteins and carbohydrates in food alters the expression of many epigenetic factors (chromatin binding, histone regulators, histone modifiers, etc.) with correlated modifications in the expression of genes involved in immunity, neurotransmission, neurodevelopment, oxidative stress, and metabolism [117]. Remarkably, these changes in expression persist for two generations even if flies are grown on a standard diet. ...
Drosophila melanogaster has played a paramount role in epigenetics, the study of changes in gene function inherited through mitosis or meiosis that are not due to changes in the DNA sequence. By analyzing simple phenotypes, such as the bristle position or cuticle pigmentation, as read-outs of regulatory processes, the identification of mutated genes led to the discovery of major chromatin regulators. These are often conserved in distantly related organisms such as vertebrates or even plants. Many of them deposit, recognize, or erase post-translational modifications on histones (histone marks). Others are members of chromatin remodeling complexes that move, eject, or exchange nucleosomes. We review the role of D. melanogaster research in three epigenetic fields: Heterochromatin formation and maintenance, the repression of transposable elements by piRNAs, and the regulation of gene expression by the antagonistic Polycomb and Trithorax complexes. We then describe how genetic tools available in D. melanogaster allowed to examine the role of histone marks and show that some histone marks are dispensable for gene regulation, whereas others play essential roles. Next, we describe how D. melanogaster has been particularly important in defining chromatin types, higher-order chromatin structures, and their dynamic changes during development. Lastly, we discuss the role of epigenetics in a changing environment.
... Altogether, the composition of the developmental diet has far-reaching consequences for Drosophila fitness. Nevertheless, there are only a few experimental studies in fruit flies [22,23], which had tested the adaptive significance of phenotypic changes caused by the developmental diet in the context of adult nutritional environments. It is therefore still an open question, whether such changes represent adaptive responses to the given developmental diet, as suggested, for example, by the PAR hypothesis, or rather are inevitable consequences of development under sub-optimal conditions. ...
Background:
The adaptive significance of phenotypic changes elicited by environmental conditions experienced early in life has long attracted attention in evolutionary biology. In this study, we used Drosophila melanogaster to test whether the developmental diet produces phenotypes better adapted to cope with similar nutritional conditions later in life. To discriminate among competing hypotheses on the underlying nature of developmental plasticity, we employed a full factorial design with several developmental and adult diets. Specifically, we examined the effects of early- and late-life diets (by varying their yeast and sugar contents) on reproductive fitness and on the amount of energy reserves (fat and glycogen) in two wild-caught populations.
Results:
We found that individuals that had developed on either low-yeast or high-sugar diet showed decreased reproductive performance regardless of their adult nutritional environment. The lower reproductive fitness might be caused by smaller body size and reduced ovariole number. Overall, these results are consistent with the silver spoon concept, which posits that development in a suboptimal environment negatively affects fitness-associated traits. On the other hand, the higher amount of energy reserves (fat) in individuals that had developed in a suboptimal environment might represent either an adaptive response or a side-effect of compensatory feeding.
Conclusion:
Our findings suggest that the observed differences in the adult physiology induced by early-life diet likely result from inevitable and general effects of nutrition on the development of reproductive and metabolic organs, rather than from adaptive mechanisms.
... In support, we found no impairment of BTZ binding in isolated proteasomes from G80-BTZ flies, in which the acquired mild resistance to BTZ likely relates to sustained upregulation of proteostatic modules; these adaptations were largely evident in G80 flies suggesting a carry-over effect. Indeed, it has been found that upon reversion to standard nutrition, flies whose prior generations have been exposed to a high-protein diet displayed multigenerational inheritance of altered gene expression [38]. Moreover, populations of Drosophila subobscura retain signatures from past contamination events with heavy metals [39], while exposure to G418 stress reduces the maternal levels of polycomb in the offspring embryos; this reduction contributed to the inheritance of induced gene expression patterns [40]. ...
Being an assembly of highly sophisticated protein machines, cells depend heavily on proteostatic modules functionality and on adequate supply of energetic molecules for maintaining proteome stability. Yet, our understanding of the adaptations induced by multigenerational proteotoxic stress is limited. We report here that multigenerational (>80 generations) proteotoxic stress in Oregon R flies induced by constant exposure to developmentally nonlethal doses of the proteasome inhibitor bortezomib (BTZ) ( G80-BTZ flies) increased proteome instability and redox imbalance, reduced fecundity and body size, and caused neuromuscular defects; it also accelerated aging. G80-BTZ flies were mildly resistant to increased doses of BTZ and showed no age-related loss of proteasome activity; these adaptations correlated with sustained upregulation of proteostatic modules, which however occurred at the cost of minimal responses to increased BTZ doses and increased susceptibility to various types of additional proteotoxic stress, namely, autophagy inhibition or thermal stress. Multigenerational proteome instability and redox imbalance also caused metabolic reprogramming being evidenced by altered mitochondrial biogenesis and suppressed insulin/IGF-like signaling (IIS) in G80-BTZ flies. The toxic effects of multigenerational proteome instability could be partially mitigated by a low-protein diet that extended G80-BTZ flies’ longevity. Overall, persistent proteotoxic stress triggers a highly conserved adaptive metabolic response mediated by the IIS pathway, which reallocates resources from growth and longevity to somatic preservation and stress tolerance. Yet, these trade-off adaptations occur at the cost of accelerated aging and/or reduced tolerance to additional stress, illustrating the limited buffering capacity of survival pathways.
... Studying diet-related effects on epigenetic mechanisms in fruit flies has just recently started [64,65]. The administration of diets with a varying macronutrient composition shows persistent changes of genes associated with epigenetic mechanisms over generations [64]. ...
... Studying diet-related effects on epigenetic mechanisms in fruit flies has just recently started [64,65]. The administration of diets with a varying macronutrient composition shows persistent changes of genes associated with epigenetic mechanisms over generations [64]. A study by Lian and co-workers [65] looked into the DNA methylation pattern of flies reared under dietary restriction. ...
Nutrigenomics explains the interaction between the genome, the proteome, the epigenome, the metabolome, and the microbiome with the nutritional environment of an organism. It is therefore situated at the interface between an organism’s health, its diet, and the genome.
The diet and/or specific dietary compounds are able to affect not only the gene expression patterns, but also the epigenetic mechanisms as well as the production of metabolites and the bacterial composition of the microbiota. Drosophila melanogaster provides a well-suited model organism to unravel these interactions in the context of nutrigenomics as it combines several advantages including an affordable maintenance, a short generation time, a high fecundity, a relatively short life expectancy, a well-characterized genome, and the availability of several mutant fly lines. Furthermore, it hosts a mammalian-like intestinal system with a clear microbiota and a fat body resembling the adipose tissue with liver-equivalent oenocytes, supporting the fly as an excellent model organism not only in nutrigenomics but also in nutritional research. Experimental approaches that are essentially needed in nutrigenomic research, including several sequencing technologies, have already been established in the fruit fly. However, studies investigating the interaction of a specific diet and/or dietary compounds in the fly are currently very limited.
The present review provides an overview of the fly’s morphology including the intestinal microbiome and antimicrobial peptides as modulators of the immune system. Additionally, it summarizes nutrigenomic approaches in the fruit fly helping to elucidate host-genome interactions with the nutritional environment in the model organism Drosophila melanogaster.
... Regarding inheritance of cold-induced effects as demonstrated by Zare et al. [1], it is essentially intergenerational, not transgenerational, as claimed, since only the first unexposed generation has been investigated. Given the profound current interest in transgenerational epigenetic inheritance [5][6][7], demonstration of which requires phenotypic analysis of at least a second unexposed generation [8], it will be compelling to examine if cold-induced effects in flies extend beyond the first unexposed generation. Notably, intergenerational inheritance of cold-induced effects has also been recently shown in mice [9]. ...
... with transcriptomic and metabolomic reorganization in D. melanogaster [10], we performed another gene overlap analysis to identify a candidate metabolic trait that might be inherited. In this analysis, differential genes related to cold treatment [1] were compared with that related to feeding of high-sugar [11,12], high-fat [13], and high-protein [8] diets, and to functional studies of the metabolic genes Hnf4 [14], Sirt1 [15], Atf3 [16], and Hr96 [17,18]. Together, triglyceride (TAG) level was identified as a promising candidate for phenotypic analysis in transgenerational experiments. ...
... Gene expression data related to various studies [1][2][3][4]8,[11][12][13][14][15][16][17][18] were used for gene overlap analysis, as outlined in Fig. 1A. Considering the advantage of larger gene numbers to gain statistical strength in overlap analysis [19], we either used the author identified genes, if available in full, or applied the interactive web tool GEO2R (www.ncbi.nlm.nih.gov/geo/ge ...
Intergenerational inheritance of transcriptional responses induced by low temperature rearing has recently been shown in Drosophila. Besides germline inheritance, faecal transfer experiments indirectly suggested that the acquired microbiome may also have contributed to the transcriptional responses in offspring. Here, we analyze expression data on inheritance of the cold‐induced effects in conjunction with previously reported transcriptomic differences between flies with a microbiota or axenic flies and provide support for a contribution of the acquired microbiome to the offspring phenotype. Also, based on a similar analysis in conjunction with diet‐ and metabolism‐related fly transcriptome data, we predicted and, then, experimentally confirmed that cold regulates triglyceride levels both inter‐ as well as trans‐generationally. This article is protected by copyright. All rights reserved.
... Various combinations of active and repressive histone modifications define chromatin states that are linked to gene function [15][16][17]. These modifications can remain during cell division, leaving a record of gene activity, i.e., epigenetic memory, that affects or primes the transcriptional response later in life [12,[18][19][20][21][22][23][24]. In mosquitoes, despite their relevance to human health, there is very little knowledge of chromatin regulation and its link to mosquito immunity, physiology and behavior [25]. ...
Background
Infection by the human malaria parasite leads to important changes in mosquito phenotypic traits related to vector competence. However, we still lack a clear understanding of the underlying mechanisms and, in particular, of the epigenetic basis for these changes. We have examined genome-wide distribution maps of H3K27ac, H3K9ac, H3K9me3 and H3K4me3 by ChIP-seq and the transcriptome by RNA-seq, of midguts from Anopheles gambiae mosquitoes blood-fed uninfected and infected with natural isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso.
Results
We report 15,916 regions containing differential histone modification enrichment between infected and uninfected, of which 8339 locate at promoters and/or intersect with genes. The functional annotation of these regions allowed us to identify infection-responsive genes showing differential enrichment in various histone modifications, such as CLIP proteases, antimicrobial peptides-encoding genes, and genes related to melanization responses and the complement system. Further, the motif analysis of regions differentially enriched in various histone modifications predicts binding sites that might be involved in the cis-regulation of these regions, such as Deaf1, Pangolin and Dorsal transcription factors (TFs). Some of these TFs are known to regulate immunity gene expression in Drosophila and are involved in the Notch and JAK/STAT signaling pathways.
Conclusions
The analysis of malaria infection-induced chromatin changes in mosquitoes is important not only to identify regulatory elements and genes underlying mosquito responses to P. falciparum infection, but also for possible applications to the genetic manipulation of mosquitoes and to other mosquito-borne systems.
Electronic supplementary material
The online version of this article (10.1186/s13072-018-0250-9) contains supplementary material, which is available to authorized users.
