Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution

Suresh, Hamsini, Crow, Megan, Jorstad, Nikolas, Hodge, Rebecca, Lein, Ed, Dobin, Alexander, Bakken, Trygve, Gillis, Jesse (September 2023) Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution. Nature Ecology and Evolution. ISSN 2397-334X

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Abstract

Enhanced cognitive function in humans is hypothesized to result from cortical expansion and increased cellular diversity. However, the mechanisms that drive these phenotypic innovations remain poorly understood, in part because of the lack of high-quality cellular resolution data in human and non-human primates. Here, we take advantage of single-cell expression data from the middle temporal gyrus of five primates (human, chimp, gorilla, macaque and marmoset) to identify 57 homologous cell types and generate cell type-specific gene co-expression networks for comparative analysis. Although orthologue expression patterns are generally well conserved, we find 24% of genes with extensive differences between human and non-human primates (3,383 out of 14,131), which are also associated with multiple brain disorders. To assess the functional significance of gene expression differences in an evolutionary context, we evaluate changes in network connectivity across meta-analytic co-expression networks from 19 animals. We find that a subset of these genes has deeply conserved co-expression across all non-human animals, and strongly divergent co-expression relationships in humans (139 out of 3,383, <1% of primate orthologues). Genes with human-specific cellular expression and co-expression profiles (such as NHEJ1, GTF2H2, C2 and BBS5) typically evolve under relaxed selective constraints and may drive rapid evolutionary change in brain function.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organism description > animal > mammal organism description > animal > mammal > primates bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Dobin, Alexander Gillis, Jesse Suresh, Hamsini
Communities:	CSHL labs > Gillis Lab CSHL labs > Dobin Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	4 September 2023
Date Deposited:	20 Sep 2023 13:29
Last Modified:	11 Jan 2024 14:27
PMCID:	PMC10627823
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40927

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