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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (bulk RNA-seq)

ABSTRACT: Here we characterize microglia transcriptional program across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to human, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, while humans express significant microglia heterogeneity. In addition, we observed notable differences in complement, phagocytic and several critical signaling pathways that are enriched with susceptibility genes to brain disorders, including Alzheimer’s and Parkinson’s disease in microglia of common animal models as compared to human. Our study provides an essential resource of conserved and divergent microglia pathways across evolution with important implications for future development of microglia-based therapies in humans.

ORGANISM(S): Mesocricetus auratus Callithrix jacchus Ovis aries Rattus norvegicus Danio rerio Mus musculus Gallus gallus Homo sapiens Macaca fascicularis

PROVIDER: GSE134706 | GEO | 2019/12/12

REPOSITORIES: GEO

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (scRNA-seq)

Project description:Here we characterize microglia transcriptional program across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to human, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, while humans express significant microglia heterogeneity. In addition, we observed notable differences in complement, phagocytic and several critical signaling pathways that are enriched with susceptibility genes to brain disorders, including Alzheimer’s and Parkinson’s disease in microglia of common animal models as compared to human. Our study provides an essential resource of conserved and divergent microglia pathways across evolution with important implications for future development of microglia-based therapies in humans.

2019-12-12 | GSE134705 | GEO

Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program

Project description:Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program

| PRJNA556197 | ENA

Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (scRNA-seq)

Project description:Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (scRNA-seq)

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (bulk RNA-seq)

Project description:Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (bulk RNA-seq)

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Conservation of human microsatellites across 450 million years of evolution.

Project description:The sequencing and comparison of vertebrate genomes have enabled the identification of widely conserved genomic elements. Chief among these are genes and cis-regulatory regions, which are often under selective constraints that promote their retention in related organisms. The conservation of elements that either lack function or whose functions are yet to be ascribed has been relatively little investigated. In particular, microsatellites, a class of highly polymorphic repetitive sequences considered by most to be neutrally evolving junk DNA that is too labile to be maintained in distant species, have not been comprehensively studied in a comparative genomic framework. Here, we used the UCSC alignment of the human genome against those of 11 mammalian and five nonmammalian vertebrates to identify and examine the extent of conservation of human microsatellites in vertebrate genomes. Out of 696,016 microsatellites found in human sequences, 85.39% were conserved in at least one other species, whereas 28.65% and 5.98% were found in at least one and three nonprimate species, respectively. An exponential decline of microsatellite conservation with increasing evolutionary time, a comparable distribution of conserved versus nonconserved microsatellites in the human genome, and a positive correlation between microsatellite conservation and overall sequence conservation, all suggest that most microsatellites are only maintained in genomes by chance, although exceptionally conserved human microsatellites were also found in distant mammals and other vertebrates. Our findings provide the first comprehensive survey of microsatellite conservation across deep evolutionary timescales, in this case 450 Myr of vertebrate evolution, and provide new tools for the identification of functional conserved microsatellites, the development of cross-species microsatellite markers and the study of microsatellite evolution above the species level.

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A 450 million years long latitudinal gradient in age-dependent extinction.

Project description:Leigh Van Valen famously stated that under constant conditions extinction probability is independent of species age. To test this 'law of constant extinction', we developed a new method using deep learning to infer age-dependent extinction and analysed 450 myr of marine life across 21 invertebrate clades. We show that extinction rate significantly decreases with age in > 90% of the cases, indicating that most species died out soon after their appearance while those which survived experienced ever decreasing extinction risk. This age-dependent extinction pattern is stronger towards the Equator and holds true when the potential effects of mass extinctions and taxonomic inflation are accounted for. These results suggest that the effect of biological interactions on age-dependent extinction rate is more intense towards the tropics. We propose that the latitudinal diversity gradient and selection at the species level account for this exceptional, yet little recognised, macroevolutionary and macroecological pattern.

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-12 | GSE134707 | GEO

A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

Project description:Despite anatomical similarities, there are differences in susceptibility to cardiovascular disease (CVD) between primates; humans are prone to myocardial ischemia, while chimpanzees are prone to myocardial fibrosis. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) allow for direct inter-species comparisons of the gene regulatory response to CVD-relevant perturbations such as oxygen deprivation, a consequence of ischemia. To gain insight into the evolution of disease susceptibility, we characterized gene expression levels in iPSC-CMs in humans and chimpanzees, before and after hypoxia and re-oxygenation. The transcriptional response to hypoxia is generally conserved across species, yet we were able to identify hundreds of species-specific regulatory responses including in genes previously associated with CVD. The 1,920 genes that respond to hypoxia in both species are enriched for loss-of-function intolerant genes; but are depleted for expression quantitative trait loci and cardiovascular-related genes. Our results indicate that response to hypoxic stress is highly conserved in humans and chimpanzees.

2019-04-10 | GSE117192 | GEO

A conserved transcriptional program for MAIT cells across mammalian evolution [Oaries_thymus_MAIT]

Project description:Mucosal-Associated Invariant T (MAIT) cells recognize the riboflavin pathway-derived metabolite 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) presented by the MHC-Ib molecule MR1. Both MR1 and the T cell receptor genes used by MAIT cells are under strong evolutionary pressure in mammals, suggesting an important role of 5-OP-RU-specific T cells across species. In humans and mice, MAIT cells acquire distinctive effector functions linked to the expression of the master transcription factor ZBTB16 (PLZF) during thymic development. Conservation of a unique differentiation program in 5-OP-RU-specific T cells from other species is unclear. Here, we used single-cell RNA sequencing to characterize the development of 5-OP-RU-specific T cells in 6 species spanning 110 million years of mammalian evolution. Cross-species comparative analyses revealed a conserved sequence of transcriptional events underlying the maturation of 5-OP-RU-specific thymocytes, marked by the early expression of ZBTB16 in all species. MAIT cells also co-expressed the transcription factors TBX21 (Tbet) and RORC (RORgt) in human, sheep, cattle and opossum. By contrast, Tbet and RORgt were expressed by distinct subsets of MAIT cells in the thymus of rodents, including pet mice and >30 genetically diverse mouse strains, dismissing a laboratory mouse artifact. In mice, RORgt+ MAIT cells further matured in the mesenteric lymph nodes and intestines to acquire a transcriptional program remarkably conserved in MAIT cells from non-rodent species and characterized by co-expression of type 1 and type 17 effector genes, but also genes associated with cytotoxicity and tissue repair. Thus, we define a deeply conserved transcriptional program for 5-OP-RU-specific T cells, which may help understand their functions.

2023-12-04 | GSE239554 | GEO

A conserved transcriptional program for MAIT cells across mammalian evolution [Mmusculus_Colon_MAIT]

2023-12-04 | GSE239553 | GEO