Project description:DNA methylation is an important chromatin modification that is necessary for the structural integrity and proper regulation of the genome for many species. Despite its conservation across the tree of life, little is known about its contribution to complex traits. Reports that differences in DNA methylation between castes in closely related Hymenopteran insects (ants, bees and wasps) contributes to social behaviors has generated hypotheses on the role of DNA methylation in governing social behavior. However, social behavior has evolved multiple times across insecta, and a common role of DNA methylation in social behavior remains outstanding. Using phylogenetic comparative methods we sought to better understand patterns of DNA methylation and social behavior across insects. DNA methylation can be found in social and solitary insects from all orders, except Diptera (flies), which suggests a shared loss of DNA methylation within this order. The lack of DNA methylation is reflected in the absence of the maintenance and de novo DNA methyltransferases (DNMT) 1 and 3, respectively. Interestingly, DNA methylation is found in species without DNMT3. DNA methylation and social behavior (social/solitary) or with division of labor (caste+/caste–) for 123 insect species analyzed from 11 orders are not evolutionary dependent, which is further supported by sequencing of DNA methylomes from 40 species.
Project description:Here we reveal evidence of a shared genetic toolkit across the full spectrum of social complexity found in Vespid wasps, from simple group living where castes remain plastic throughout life, to complex superorganismal societies comprised of mutually dependent insects with irreversible castes determined during development. We generated brain transcriptomic data for castes in nine representative species; using a machine learning approach we identified thousands of shared orthologs which consistently describe castes (queens and workers), from species with the simplest (Mischocyttarus paper wasps) to the most complex (e.g. Vespine wasps) levels of social organisation. The top 400 genes were enriched in synaptic transport genes, suggesting that these changes could affect brain neural function and connectivity. Fine-scale dissection of these patterns revealed that the molecular processes underpinning the simpler societies (which likely represent the origins of social living) are conserved throughout the major transition, but that additional processes may come into play in the more complex societies, especially at the point of no return where societies transition to be committed superorganisms. These analyses provide the first evidence of a conserved toolkit regulating social behaviour across the full spectrum of social complexity in any social insect. Importantly, they also provide evidence that there may be fundamental differences discriminating superorganismal societies from non-superorganismal societies. We suggest that the evolution of irreversible caste commitment (in superorganisms) is accompanied by a fundamental shift in the underlying regulatory molecular machinery; such shifts may also typify other major evolutionary transitions that are characterised by the emergence of a committed division of labour, such as the evolution of multicellularity.
Project description:Genomic profiling of anaplastic meningioma can inform prognostic gene level alterations in lower-grade meningiomas, potentially reflecting evolution of anaplastic meningioma from lowergrade precursor tumours. Larger scale studies in paired primary and recurrent meningiomas are warranted to unravel the evolutionary path to anaplastic meningiomas and prognostic genomic alterations in detail
Project description:Single-cell sequencing has revealed cell state heterogeneity across diverse healthy and malignant tissues. However, the extent these cell states are plastic or heritable remains largely unknown. To address this, we introduce PATH (Phylogenetic Analysis of Trait Heritability), a framework to quantify cell state heritability versus plasticity and infer cell state transition and proliferation dynamics from single-cell lineage tracing data. Here, we used PATH to measure phylogenetic correlations on single-cell phylogenies derived from gliomaspheres to reveal the somatic evolutionary relationships between Neural Progenitor-like (NPC), Oligodendrocyte Progenitor-like (OPC), Astrocyte-like (AC), and Mesenchymal-like (MES) cancer cell states.
Project description:Schizophrenia is often marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well understood. Here we used a translational model of subanesthetic ketamine mice to delineate neural pathways in the brain linked to social deficits in schizophrenia. Mice treated with chronic ketamine exhibit profound social and sensorimotor deficits as previously reported. Using three-dimensional c-Fos immunolabeling and volume imaging (iDISCO), we show that ketamine treatment resulted in hypoactivation of the lateral septum (LS) in response to social stimuli. Chemogenetic activation of the LS rescued social deficits after ketamine treatment, while chemogenetic inhibition of previously active populations in the LS (i.e. social engram neurons) recapitulated social deficits in ketamine-naïve mice. We then examined the translatome of LS engram neurons and found upregulation of genes encoding potassium inwardly-rectifying channels and solute transporters as well as dysregulation of genes implicated in apoptotic processes, all of which could contribute to the hypoactivation of LS social engram neurons after chronic ketamine exposure. A number of ketamine-induced differentially expressed genes (DEGs), including those involved in mitochondrial function and neuroinflammatory pathways, were shared with human schizophrenia and mouse models of neurodevelopmental disorders.
Project description:Social interactions are typically characterised by conflict and competition. This antagonism can play a critical role in evolutionary processes, such as promoting diversity through maintenance of alternative strategies or driving accelerated evolution through arms-race like escalation. However, despite our sophisticated understanding of how conflict shapes social traits, we still have limited knowledge of how it impacts molecular evolution across the underlying ‘social genes’. To address this problem, we analysed the genome wide impact of social interactions in a microbe. To understand broad-scale processes shaping molecular evolution at social genes we have used four different, but complementary, approaches to identify sets of social genes. For ease, we have named these sets ‘sociality’, ‘chimerism’, ‘antagonism’ and ‘cheater’ genes. Chimerism genes are defined as those up-regulated in chimeric aggregations in comparison to clonal aggregations. This is based on the logic that chimeric development will be characterised by conflict, and hence these genes will show the signatures of conflict driven evolution. Using genome sequences from 67 Dictyostelium discoideum strains, we find that social genes often exhibit enhanced polymorphism and accelerated evolution. However, these patterns are not consistent with the expectation of conflict driven processes, but instead reflect relatively relaxed purifying selection. This pattern reflects the fact that social interactions are conditional, and therefore selection on genes expressed in social interactions is diluted by generations of inactivity. This results in the ‘Red King’ process, wherein dilution of selection by inactivity enhances the role of drift, resulting in increased polymorphism and accelerated evolution.
Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series
Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
Project description:E.O. Wilson proposed in Sociobiology that similarities between human and animal societies reflect common mechanistic and evolutionary roots. When introduced in 1975 this controversial hypothesis was beyond science’s ability to test and remains unproven. We used genomic analyses to determine whether superficial behavioral similarities in humans and the highly social honey bee reflect common molecular mechanisms. Here we report that gene expression signatures for individual bees unresponsive to various salient social stimuli are significantly enriched for autism spectrum disorder-related genes. These signatures occur in the mushroom bodies, a high-level integration center of the insect brain. Further, our finding of enrichment was unique to autism spectrum disorders; brain gene expression signatures from other honey bee behaviors do not show this enrichment, nor do data sets from other human behavioral and health conditions. These results demonstrate deep conservation for genes associated with a human social pathology and individual differences in insect social behavior, thus providing an example of how comparative genomics can be used to test sociobiological theory.