Gene expression in human vs chimpanzees
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ABSTRACT:
PROVIDER: PRJNA90041 | ENA |
REPOSITORIES: ENA
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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
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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:Differential gene expression in CD137HI vs CD137LO human healthy donor monocytes
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Project description:Hepatitis A virus (HAV) is a hepatotropic human picornavirus that has been associated only with acute infection. Its pathogenesis is not well understood since there have been few recent studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by qRT-PCR and examining critical aspects of the innate immune response including intrahepatic interferon-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), a hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I interferon-stimulated genes in the liver compared to chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal ISG15 and IFIT1 responses peaked 1-2 weeks after HAV challenge, then subsided despite continuing high hepatic viral loads. An acute inflammatory response at 3-4 weeks correlated with the appearance of virus-specific antibodies, and both apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after its clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 weeks) than HCV RNA in animals with acute resolving HCV infection (10-20 weeks). Collectively, these findings suggest that early HAV infection is far stealthier than HCV infection and represents a distinctly different paradigm in viral-host interactions within the liver.
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Project description:Primary outcome(s): Gene expression of targeted genes
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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:Gene expression from human iPSC derived motor neurons.
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