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The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees

ABSTRACT: We used embryoid bodies to compare differences in gene expression between humans and chimpanzees in a large number of cell types

ORGANISM(S): Homo sapiens Pan troglodytes

PROVIDER: GSE201516 | GEO | 2023/04/11

REPOSITORIES: GEO

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The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees.

Project description:BackgroundComparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues. Here, we used single-cell RNA sequencing of embryoid bodies to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees.ResultsWe find hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Using embryoid bodies from a human-chimpanzee fused cell line, we also infer the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. Using the cis/trans inference and an analysis of transcription factor binding sites, we identify dozens of transcription factors whose inter-species differences in expression are affecting expression differences between humans and chimpanzees in hundreds of target genes.ConclusionsHere, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences.

| S-EPMC10496171 | biostudies-literature

The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees

Project description:The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees

| PRJNA832107 | ENA

Age-Associated Epigenetic Change in Chimpanzees and Humans

Project description:Genome wide DNA methylation profiling of captive chimpanzees of ages spanning the chimpanzee lifespan (whole blood) Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an “epigenetic clock” to predict an individual’s chronological age within a few years. Studies of age-related epigenetic change in other mammals, including mice, whales, and canids, show that some but not all of the same loci as in humans undergo age-associated methylation changes. An in-depth comparison of chimpanzees with humans is of interest because the two species are genetically similar but differ in lifespan. To this end, we profiled genome-wide blood methylation levels for 113 samples from 83 chimpanzees aged 1-58 years (26 chimpanzees were sampled at multiple ages during their lifespan). We used this data to build a chimpanzee-specific epigenetic clock model as well as to compare genome-wide patterns of change with age between humans and chimpanzees more generally.

2020-08-23 | GSE136296 | GEO

Epigenetic aging of the prefrontal cortex and cerebellum in humans, chimpanzees, and rhesus macaques

Project description:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques

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Transcription profiling of brain in three adult humans and three adult chimpanzees

Project description:Gene expression profiling in brain of three adult humans and three adult chimpanzees

2004-05-27 | E-MEXP-43 | biostudies-arrayexpress

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.

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Divergence in alternative polyadenylation between humans and chimpanzees contributes to gene regulatory differences between species

Project description:Differences in gene regulation contribute to phenotypic differences between humans and other primates. While co-transcriptional gene regulatory mechanisms such as alternative polyadenylation (APA) can help explain how variation in gene regulation manifests, such mechanisms remain understudied. We measured polyadenylation site (PAS) usage in a panel of 6 human and 6 chimpanzee lymphoblastoid cell lines (LCLs). While APA is largely conserved between humans and chimpanzees, genes with divergent APA patterns are enriched among differentially expressed and differentially translated genes. Differential usage of 3’ UTR and intronic PAS are both significantly correlated with differential mRNA expression effect sizes but in opposite directions. For many genes, there is one PAS dominant, meaning it is used much more often than others. The dominant PAS for these gene is overwhelmingly shared between species, however, differences in dominant PAS are enriched for genes with expression differences. Finally, through post-translational mechanisms, we believe APA contributes to genes differentially expressed at the protein level but not in mRNA. As this is the first primate comparative study of APA, our study establishes APA as a key mechanism underlying the genetic regulation of gene and protein expression levels in primates.

2021-01-22 | GSE155245 | GEO

Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22

Project description:While some studies have reported gene expression differences between humans and chimpanzees, the mechanisms underlying such changes remain poorly understood. To address this issue, we examined, by MeDIP-chip, DNA methylation patterns of peripheral blood cells from age- and sex- matched human and chimpanzee individuals. Our analysis identified some differentially methylated regions between the two species and suggests that changes in DNA methylation pattern are involved in the diversification of transcriptome during evolution.

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Age-Associated Epigenetic Change in Chimpanzees and Humans

Project description:Age-Associated Epigenetic Change in Chimpanzees and Humans

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A comparative study of endoderm differentiation in humans and chimpanzees

Project description:There is substantial interest in the genetic regulatory framework that is established in early human development, and in the evolutionary forces that shaped early developmental processes in humans. Progress in these areas has been slow because it is difficult to obtain relevant biological samples. Recent technological developments in the generation and differentiation of inducible pluripotent stem cells (iPSCs) provide the ability to develop in vitro models of early human and non-human primates developmental stages. We have previously established matched iPSC panels from humans and chimpanzees. Using these panels, we comparatively characterized gene regulatory changes through a four-day timecourse differentiation of iPSCs (day 1) into primary streak (day 2), endoderm progenitors (day 3), and definitive endoderm (day 4). As might be expected, we found that differentiation stage (in effect, cell type) is the major driver of variation in gene expression levels in our study, followed by species. We then identified thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we considered gene-specific dynamic regulatory trajectories throughout the timecourse, we found that 75% of genes, including nearly all known endoderm developmental markers, have conserved trajectories in the two species. Interestingly, we observed a marked reduction of both intra- and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of variation in endoderm progenitors. The reduction in variation in gene expression levels at a specific developmental stage, paired with the high degree of conservation of temporal expression across species, is consistent with the dynamics of developmental canalization. Overall, we conclude that endoderm development in iPSC-based models are highly conserved and canalized between humans and our closest evolutionary relative.

2017-05-02 | GSE98411 | GEO

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