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

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

PROVIDER: PRJNA649122 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12337821.fastq.gz	Fastqsanger.gz
	SRR12337822.fastq.gz	Fastqsanger.gz
	SRR12337823.fastq.gz	Fastqsanger.gz
	SRR12337824.fastq.gz	Fastqsanger.gz
	SRR12337825.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

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

Project description:While comparative functional genomic studies have shown that inter-species differences in gene expression can be explained by corresponding inter-species differences in genetic and epigenetic regulatory mechanisms, co-transcriptional mechanisms, such as alternative polyadenylation (APA), have received little attention. We characterized APA in lymphoblastoid cell lines from six humans and six chimpanzees by identifying and estimating the usage for 44,432 polyadenylation sites (PAS) in 9518 genes. Although APA is largely conserved, 1705 genes showed significantly different PAS usage (FDR 0.05) between species. Genes with divergent APA also tend to be differentially expressed, are enriched among genes showing differences in protein translation, and can explain a subset of observed inter-species protein expression differences that do not differ at the transcript level. Finally, we found that genes with a dominant PAS, which is used more often than other PAS, are particularly enriched for differentially expressed genes.

| S-EPMC7954529 | biostudies-literature

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.

2012-02-02 | GSE35475 | GEO

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

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

| PRJNA152359 | 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

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

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

2023-04-11 | GSE201516 | GEO

Patterns and rates of intron divergence between humans and chimpanzees.

Project description:BackgroundIntrons, which constitute the largest fraction of eukaryotic genes and which had been considered to be neutral sequences, are increasingly acknowledged as having important functions. Several studies have investigated levels of evolutionary constraint along introns and across classes of introns of different length and location within genes. However, thus far these studies have yielded contradictory results.ResultsWe present the first analysis of human-chimpanzee intron divergence, in which differences in the number of substitutions per intronic site (Ki) can be interpreted as the footprint of different intensities and directions of the pressures of natural selection. Our main findings are as follows: there was a strong positive correlation between intron length and divergence; there was a strong negative correlation between intron length and GC content; and divergence rates vary along introns and depending on their ordinal position within genes (for instance, first introns are more GC rich, longer and more divergent, and divergence is lower at the 3' and 5' ends of all types of introns).ConclusionWe show that the higher divergence of first introns is related to their larger size. Also, the lower divergence of short introns suggests that they may harbor a relatively greater proportion of regulatory elements than long introns. Moreover, our results are consistent with the presence of functionally relevant sequences near the 5' and 3' ends of introns. Finally, our findings suggest that other parts of introns may also be under selective constraints.

| S-EPMC1852421 | biostudies-literature

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.

2019-04-10 | GSE117192 | GEO

Mouse alternative polyadenylation

Project description:Divergence of alternative polyadenylation in mouse

| PRJEB15336 | ENA

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

2021-04-07 | GSE154403 | GEO

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