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

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

PROVIDER: PRJNA556197 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12024248.fastq.gz	Fastqsanger.gz
	SRR12024249.fastq.gz	Fastqsanger.gz
	SRR12024250.fastq.gz	Fastqsanger.gz
	SRR12024251.fastq.gz	Fastqsanger.gz
	SRR12024252.fastq.gz	Fastqsanger.gz

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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 (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.

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

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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.

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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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