Divergence in alternative polyadenylation contributes to gene regulatory differences between humans and chimpanzees
- University of Chicago, United States
Abstract
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 usage for 44,432 polyadenylation sites (PAS) in 9,518 genes. Although APA is largely conserved, 1,705 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.
Data availability
Sequencing data available on GEO under accession GSE155245.
Article and author information
Author details
Briana E Mittleman
Funding
National Institutes of Health (T32GM09197)
- Briana E Mittleman
National Institutes of Health (F31HL149259)
- Briana E Mittleman
National Institutes of Health (R01HG010772)
- Yoav Gilad
National Institutes of Health (R35GM13172)
- Yoav Gilad
National Institutes of Health (K12HL119995)
- Sebastian Pott
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Graham Coop, University of California, Davis, United States
Version history
- Received: August 28, 2020
- Accepted: February 12, 2021
- Accepted Manuscript published: February 17, 2021 (version 1)
- Version of Record published: March 12, 2021 (version 2)
Copyright
© 2021, Mittleman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Divergence in alternative polyadenylation contributes to gene regulatory differences between humans and chimpanzees
eLife 10:e62548.
https://doi.org/10.7554/eLife.62548
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