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

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.

The following data sets were generated

Article and author information

Author details

  1. Briana E Mittleman

    Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4979-4652
  2. Sebastian Pott

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4118-6150
  3. Shane Warland

    Section of Genetic Medicine, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kenneth Barr

    Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0769-7053
  5. Claudia Cuevas

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yoav Gilad

    Department of Medicine, University of Chicago, Chicago, United States
    For correspondence
    gilad@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8284-8926

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

  1. Graham Coop, University of California, Davis, United States

Version history

  1. Received: August 28, 2020
  2. Accepted: February 12, 2021
  3. Accepted Manuscript published: February 17, 2021 (version 1)
  4. 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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  1. Briana E Mittleman
  2. Sebastian Pott
  3. Shane Warland
  4. Kenneth Barr
  5. Claudia Cuevas
  6. Yoav Gilad
(2021)
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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https://doi.org/10.7554/eLife.62548

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