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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

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

PROVIDER: GSE134707 | 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 (bulk RNA-seq)

2019-12-12 | GSE134706 | 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

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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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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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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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Conservation of miRNA-mediated silencing mechanisms across 600 million years of animal evolution.

Project description:Our current knowledge about the mechanisms of miRNA silencing is restricted to few lineages such as vertebrates, arthropods, nematodes and land plants. miRNA-mediated silencing in bilaterian animals is dependent on the proteins of the GW182 family. Here, we dissect the function of GW182 protein in the cnidarian Nematostella, separated by 600 million years from other Metazoa. Using cultured human cells, we show that Nematostella GW182 recruits the CCR4-NOT deadenylation complexes via its tryptophan-containing motifs, thereby inhibiting translation and promoting mRNA decay. Further, similarly to bilaterians, GW182 in Nematostella is recruited to the miRNA repression complex via interaction with Argonaute proteins, and functions downstream to repress mRNA. Thus, our work suggests that this mechanism of miRNA-mediated silencing was already active in the last common ancestor of Cnidaria and Bilateria.

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Conservation of transcription factor binding specificities across 600 million years of bilateria evolution.

Project description:Divergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data. This analysis revealed that TF binding specificities are highly conserved between Drosophila and mammals, and that for orthologous TFs, the similarity extends even to the level of very subtle dinucleotide binding preferences. The few human TFs with divergent specificities function in cell types not found in fruit flies, suggesting that evolution of TF specificities contributes to emergence of novel types of differentiated cells.

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Conservation of the regulated structure of folded myosin 2 in species separated by at least 600 million years of independent evolution.

Project description:The myosin 2 family of molecular motors includes isoforms regulated in different ways. Vertebrate smooth-muscle myosin is activated by phosphorylation of the regulatory light chain, whereas scallop striated adductor-muscle myosin is activated by direct calcium binding to its essential light chain. The paired heads of inhibited molecules from myosins regulated by phosphorylation have an asymmetric arrangement with motor-motor interactions. It was unknown whether such interactions were a common motif for inactivation used in other forms of myosin-linked regulation. Using electron microscopy and single-particle image processing, we show that indistinguishable structures are indeed found in myosins and heavy meromyosins isolated from scallop striated adductor muscle and turkey gizzard smooth muscle. The similarities extend beyond the shapes of the heads and interactions between them: In both myosins, the tail folds into three segments, apparently at identical sites; all three segments are in close association outside the head region; and two segments are associated in the same way with one head in the asymmetric arrangement. Thus, these organisms, which have different regulatory mechanisms and diverged from a common ancestor >600 Myr ago, have the same quaternary structure. Conservation across such a large evolutionary distance suggests that this conformation is of fundamental functional importance.

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