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Status |
Public on Jan 22, 2021 |
Title |
Divergence in alternative polyadenylation between humans and chimpanzees contributes to gene regulatory differences between species |
Organisms |
Pan troglodytes; Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
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.
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Overall design |
We measured polyadenylation site (PAS) usage in a panel of 6 human and 6 chimpanzee lymphoblastoid cell lines (LCLs). We collected 3' Seq on total and nuclear mRNA using the Lexogen Rev Quant Seq protocol. We collected RNA sequencing on the total mRNA using the Illumina TruSeq kit.
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Contributor(s) |
Mittleman B, Pott S, Warland S, Barr K, Cuevas C, Gilad Y |
Citation(s) |
33595436 |
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Submission date |
Jul 28, 2020 |
Last update date |
Mar 23, 2021 |
Contact name |
Yoav GiladLi |
E-mail(s) |
gilad@uchicago.edu
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Organization name |
University of Chicago
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Department |
Section of Genetic Medicine
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Lab |
Gilad
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Street address |
920 e 58th St
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City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60637 |
Country |
USA |
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Platforms (3) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL21121 |
Illumina NextSeq 500 (Pan troglodytes) |
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Samples (23)
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Relations |
BioProject |
PRJNA649122 |
SRA |
SRP273904 |