Age-Associated Epigenetic Change in Chimpanzees and Humans
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ABSTRACT:
PROVIDER: PRJNA562025 | ENA |
REPOSITORIES: ENA
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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
Project description: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 to within a few years. Here, we examined how the pattern of epigenetic ageing in chimpanzees compares with humans. We profiled genome-wide blood methylation levels by microarray for 113 samples from 83 chimpanzees aged 1-58 years (26 chimpanzees were sampled at multiple ages during their lifespan). Many sites (greater than 65 000) showed significant change in methylation with age and around one-third (32%) of these overlap with sites showing significant age-related change in humans. At over 80% of sites showing age-related change in both species, chimpanzees displayed a significantly faster rate of age-related change in methylation than humans. We also built a chimpanzee-specific epigenetic clock that predicted age in our test dataset with a median absolute deviation from known age of only 2.4 years. However, our chimpanzee clock showed little overlap with previously constructed human clocks. Methylation at CpGs comprising our chimpanzee clock showed moderate heritability. Although the use of a human microarray for profiling chimpanzees biases our results towards regions with shared genomic sequence between the species, nevertheless, our results indicate that there is considerable conservation in epigenetic ageing between chimpanzees and humans, but also substantial divergence in both rate and genomic distribution of ageing-associated sites. This article is part of the theme issue 'Evolution of the primate ageing process'.
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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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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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Project description:We used embryoid bodies to compare differences in gene expression between humans and chimpanzees in a large number of cell types
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Project description:Despite the close evolutionary relationship and striking genetic similarity between humans and chimpanzees, there are remarkable differences in anatomy, behavior, and disease susceptibility in the two species. One step towards understanding the biological basis of these phenotypic differences is to characterize quantitative differences in levels of expression of genes in humans and chimpanzees. To contribute to such analysis, we compared gene expression patterns in lymphoblastoid cell lines between nine unrelated humans and ten unrelated chimpanzees by using human cDNA microarrays. Hybridizations to arrays containing 43,233 features produced high quality data for 22,879 cDNA clones, representing 20,266 Unigenes. We observed statistically significant differences in transcript levels for 32% of these genes (P < 0.05, Student t test), with about 200 cDNAs showing differences of more than 2-fold (lower bounds of 95% confidence interval). Among these are genes involved in cell surface glycosylation and responses to toxins and viruses. Examination of functional annotations for the differentially expressed genes revealed lower expression of cell cycle and energy pathways genes, and higher expression of chemokines, 26S proteasome and cell motility genes in chimpanzee samples. These genes and pathways could underlie some of the phenotypic differences between humans and chimpanzees. Keywords: other
2005-06-08 | GSE1464 | GEO
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.
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