Structure and function of gene regulatory networks associated with worker sterility in honeybees.
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ABSTRACT:
SUBMITTER: Sobotka JA
PROVIDER: S-EPMC4755009 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe evolution of reproductive self-sacrifice is well understood from kin theory, yet our understanding of how actual genes influence the expression of reproductive altruism is only beginning to take shape. As a model in the molecular study of social behaviour, the honey bee Apis mellifera has yielded hundreds of genes associated in their expression with differences in reproductive status of females, including genes directly associated with sterility, yet there has not been an attempt to link these candidates into functional networks that explain how workers regulate sterility in the presence of queen pheromone. In this study we use available microarray data and a co-citation analysis to describe what gene interactions might regulate a worker's response to ovary suppressing queen pheromone.ResultsWe reconstructed a total of nine gene networks that vary in size and gene composition, but that are significantly enriched for genes of reproductive function. The networks identify, for the first time, which candidate microarray genes are of functional importance, as evidenced by their degree of connectivity to other genes within each of the inferred networks. Our study identifies single genes of interest related to oogenesis, including eggless, and further implicates pathways related to insulin, ecdysteroid, and dopamine signaling as potentially important to reproductive decision making in honey bees.ConclusionsThe networks derived here appear to be variable in gene composition, hub gene identity, and the overall interactions they describe. One interpretation is that workers use different networks to control personal reproduction via ovary activation, perhaps as a function of age or environmental circumstance. Alternatively, the multiple networks inferred here may represent segments of the larger, single network that remains unknown in its entirety. The networks generated here are provisional but do offer a new multi-gene framework for understanding how honey bees regulate personal reproduction within their highly social breeding system.
| S-EPMC4030028 | biostudies-literature
Project description:Inference of biological network structures is often performed on high-dimensional data, yet is hindered by the limited sample size of high throughput "omics" data typically available. To overcome this challenge, often referred to as the "small n, large p problem," we exploit known organizing principles of biological networks that are sparse, modular, and likely share a large portion of their underlying architecture. We present SHINE-Structure Learning for Hierarchical Networks-a framework for defining data-driven structural constraints and incorporating a shared learning paradigm for efficiently learning multiple Markov networks from high-dimensional data at large p/n ratios not previously feasible. We evaluated SHINE on Pan-Cancer data comprising 23 tumor types, and found that learned tumor-specific networks exhibit expected graph properties of real biological networks, recapture previously validated interactions, and recapitulate findings in literature. Application of SHINE to the analysis of subtype-specific breast cancer networks identified key genes and biological processes for tumor maintenance and survival as well as potential therapeutic targets for modulating known breast cancer disease genes.
| S-EPMC10231840 | biostudies-literature
Project description:Several lines of evidence support genetic links between ovary size and division of labor in worker honey bees. However, it is largely unknown how ovaries influence behavior. To address this question, we first performed transcriptional profiling on worker ovaries from two genotypes that differ in social behavior and ovary size. Then, we contrasted the differentially expressed ovarian genes with six sets of available brain transcriptomes. Finally, we probed behavior-related candidate gene networks in wild-type ovaries of different sizes. We found differential expression in 2151 ovarian transcripts in these artificially selected honey bee strains, corresponding to approximately 20.3% of the predicted gene set of honey bees. Differences in gene expression overlapped significantly with changes in the brain transcriptomes. Differentially expressed genes were associated with neural signal transmission (tyramine receptor, TYR) and ecdysteroid signaling; two independently tested nuclear hormone receptors (HR46 and ftz-f1) were also significantly correlated with ovary size in wild-type bees. We suggest that the correspondence between ovary and brain transcriptomes identified here indicates systemic regulatory networks among hormones (juvenile hormone and ecdysteroids), pheromones (queen mandibular pheromone), reproductive organs and nervous tissues in worker honey bees. Furthermore, robust correlations between ovary size and neuraland endocrine response genes are consistent with the hypothesized roles of the ovaries in honey bee behavioral regulation.
| S-EPMC3233392 | biostudies-literature
Project description:BACKGROUND:Melissococcus plutonius is an entomopathogenic bacterium that causes European foulbrood (EFB), a honeybee (Apis mellifera L.) disease that necessitates quarantine in some countries. In Czechia, positive evidence of EFB was absent for almost 40 years, until an outbreak in the Krkonose Mountains National Park in 2015. This occurrence of EFB gave us the opportunity to study the epizootiology of EFB by focusing on the microbiome of honeybee workers, which act as vectors of honeybee diseases within and between colonies. METHODS:The study included worker bees collected from brood combs of colonies (i) with no signs of EFB (EFB0), (ii) without clinical symptoms but located at an apiary showing clinical signs of EFB (EFB1), and (iii) with clinical symptoms of EFB (EFB2). In total, 49 samples from 27 honeybee colonies were included in the dataset evaluated in this study. Each biological sample consisted of 10 surface-sterilized worker bees processed for DNA extraction. All subjects were analyzed using conventional PCR and by metabarcoding analysis based on the 16S rRNA gene V1-V3 region, as performed through Illumina MiSeq amplicon sequencing. RESULTS:The bees from EFB2 colonies with clinical symptoms exhibited a 75-fold-higher incidence of M. plutonius than those from EFB1 asymptomatic colonies. Melissococcus plutonius was identified in all EFB1 colonies as well as in some of the control colonies. The proportions of Fructobacillus fructosus, Lactobacillus kunkeei, Gilliamella apicola, Frischella perrara, and Bifidobacterium coryneforme were higher in EFB2 than in EFB1, whereas Lactobacillus mellis was significantly higher in EFB2 than in EFB0. Snodgrassella alvi and L. melliventris, L. helsingborgensis and, L. kullabergensis exhibited higher proportion in EFB1 than in EFB2 and EFB0. The occurrence of Bartonella apis and Commensalibacter intestini were higher in EFB0 than in EFB2 and EFB1. Enterococcus faecalis incidence was highest in EFB2. CONCLUSIONS:High-throughput Illumina sequencing permitted a semi-quantitative analysis of the presence of M. plutonius within the honeybee worker microbiome. The results of this study indicate that worker bees from EFB-diseased colonies are capable of transmitting M. plutonius due to the greatly increased incidence of the pathogen. The presence of M. plutonius sequences in control colonies supports the hypothesis that this pathogen exists in an enzootic state. The bacterial groups synergic to both the colonies with clinical signs of EFB and the EFB-asymptomatic colonies could be candidates for probiotics. This study confirms that E. faecalis is a secondary invader to M. plutonius; however, other putative secondary invaders were not identified in this study.
| S-EPMC5619233 | biostudies-literature
Project description:The honeybee is the primary managed species worldwide for both crop pollination and honey production. Owing to beekeeping activity, its high relative abundance potentially affects the structure and functioning of pollination networks in natural ecosystems. Given that evidences about beekeeping impacts are restricted to observational studies of specific species and theoretical simulations, we still lack experimental data to test for their larger-scale impacts on biodiversity. Here we used a three-year field experiment in a natural ecosystem to compare the effects of pre- and post-establishment stages of beehives on the pollination network structure and plant reproductive success. Our results show that beekeeping reduces the diversity of wild pollinators and interaction links in the pollination networks. It disrupts their hierarchical structural organization causing the loss of interactions by generalist species, and also impairs pollination services by wild pollinators through reducing the reproductive success of those plant species highly visited by honeybees. High-density beekeeping in natural areas appears to have lasting, more serious negative impacts on biodiversity than was previously assumed.
| S-EPMC6423295 | biostudies-literature
Project description:Gene regulatory networks allow the control of gene expression patterns in living cells. The study of network topology has revealed that certain subgraphs of interactions or "motifs" appear at anomalously high frequencies. We ask here whether this phenomenon may emerge because of the functions carried out by these networks. Given a framework for describing regulatory interactions and dynamics, we consider in the space of all regulatory networks those that have prescribed functional capabilities. Markov Chain Monte Carlo sampling is then used to determine how these functional networks lead to specific motif statistics in the interactions. In the case where the regulatory networks are constrained to exhibit multistability, we find a high frequency of gene pairs that are mutually inhibitory and self-activating. In contrast, networks constrained to have periodic gene expression patterns (mimicking for instance the cell cycle) have a high frequency of bifan-like motifs involving four genes with at least one activating and one inhibitory interaction.
| S-EPMC3198326 | biostudies-literature
Project description:The hypopharyngeal glands (HPGs) of worker honeybees undergo physiological changes along with the age-dependent role change from nursing to foraging: nurse bee HPGs secrete mainly major royal jelly proteins, whereas forager HPGs secrete mainly ?-glucosidase III, which converts the sucrose in the nectar into glucose and fructose. We previously identified two other genes, Apis mellifera buffy (Ambuffy) and Apis mellifera matrix metalloproteinase 1 (AmMMP1), with enriched expression in nurse bee and forager HPGs, respectively. In the present study, to clarify the molecular mechanisms that coordinate HPG physiology with worker behavior, we first analyzed whether Ambuffy, AmMMP1, mrjp2 (a gene encoding one of major royal jelly protein isoforms), and Hbg3 (a gene encoding ?-glucosidase III) expression, is associated with worker behavior in 'single-cohort colonies' where workers of almost the same age perform different tasks. Expression of these genes correlated with the worker's role, while controlling for age, indicating their regulation associated with the worker's behavior. Associated gene expression suggested the possible involvement of some hormonal factors in its regulation. We therefore examined the relationship between ecdysone- and juvenile hormone (JH)-signaling, and the expression profiles of these 'indicator' genes (nurse bee HPG-selective genes: mrjp2 and Ambuffy, and forager HPG-selective genes: Hbg3 and AmMMP1). Expression of both ecdysone-regulated genes (ecdysone receptor, mushroom body large type Kenyon cell specific protein-1, and E74) and JH-regulated genes (Methoprene tolerant and Krüppel homolog 1) was higher in the forager HPGs than in the nurse bee HPGs, suggesting the possible roles of ecdysone- and JH-regulated genes in worker HPGs. Furthermore, 20-hydroxyecdysone-treatment repressed both nurse bee- and forager-selective gene expression, whereas methoprene-treatment enhanced the expression of forager-selective genes and repressed nurse bee-selective genes in the HPGs. Our findings suggest that both ecdysone- and JH-signaling cooperatively regulate the physiological state of the HPGs in association with the worker's behavior.
| S-EPMC4470657 | biostudies-literature
Project description:Highly social insects are characterized by caste dimorphism, with distinct size differences of reproductive organs between fertile queens and the more or less sterile workers. An abundance of nutrition or instruction via diet-specific compounds has been proposed as explanations for the nutrition-driven queen and worker polyphenism. Here, we further explored these models in the honeybee (Apis mellifera) using worker nutrition rearing and a novel mutational screening approach using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) method. The worker nutrition-driven size reduction of reproductive organs was restricted to the female sex, suggesting input from the sex determination pathway. Genetic screens on the sex determination genes in genetic females for size polyphenism revealed that doublesex (dsx) mutants display size-reduced reproductive organs irrespective of the sexual morphology of the organ tissue. In contrast, feminizer (fem) mutants lost the response to worker nutrition-driven size control. The first morphological worker mutants in honeybees demonstrate that the response to nutrition relies on a genetic program that is switched "ON" by the fem gene. Thus, the genetic instruction provided by the fem gene provides an entry point to genetically dissect the underlying processes that implement the size polyphenism.
| S-EPMC6428258 | biostudies-literature
Project description:BACKGROUND: Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. RESULTS: Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. CONCLUSIONS: The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cycle related genes could be key mechanism for TNT induced liver toxicity.
| S-EPMC2998496 | biostudies-literature
Project description:We show that differences in the reproductive development of honey bee workers are associated with locus-specific changes to abundance of messenger RNA. Using a cross-fostering field experiment to control for differences related to age and environment, we compared the gene expression profiles of functionally sterile workers (wild-type) and those from a mutant strain in which workers are reproductively active (anarchist). Among the set of three genes that are significantly differentially expressed are two major royal jelly proteins that are up-regulated in wild-type heads. This discovery is consistent with sterile workers synthesizing royal jelly as food for developing brood. Likewise, the relative underexpression of these two royal jellies in anarchist workers is consistent with these workers' characteristic avoidance of alloparental behaviour, in favour of selfish egg-laying. Overall, there is a trend for the most differentially expressed genes to be up-regulated in wild-type workers. This pattern suggests that functional sterility in honey bee workers may generally involve the expression of a suite of genes that effectively 'switch' ovaries off, and that selfish reproduction in honey bee workers, though rare, is the default developmental pathway that results when ovary activation is not suppressed.
| S-EPMC1847478 | biostudies-literature