Gene expression variability in human and chimpanzee populations share common determinants

  1. Benjamin Jung Fair  Is a corresponding author
  2. Lauren E Blake
  3. Abhishek Sarkar
  4. Bryan J Pavlovic
  5. Claudia Cuevas
  6. Yoav Gilad  Is a corresponding author
  1. University of Chicago, United States
  2. University of California, San Francisco, United States

Abstract

Inter-individual variation in gene expression has been shown to be heritable and is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.

Data availability

RNA-Seq data available under GEO accession number GSE151397. Raw whole genome sequencing data under SRA accession PRJNA635393. Processed whole genome sequencing data available as variant calls at European variation archive, EVA accession PRJEB39475.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Benjamin Jung Fair

    Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, United States
    For correspondence
    bjf79@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6296-5703
  2. Lauren E Blake

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Abhishek Sarkar

    Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bryan J Pavlovic

    Department of Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7751-5315
  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 Institute of General Medical Sciences (R35GM131726)

  • Yoav Gilad

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Fair 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.

Metrics

  • 4,721
    views
  • 401
    downloads
  • 38
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Benjamin Jung Fair
  2. Lauren E Blake
  3. Abhishek Sarkar
  4. Bryan J Pavlovic
  5. Claudia Cuevas
  6. Yoav Gilad
(2020)
Gene expression variability in human and chimpanzee populations share common determinants
eLife 9:e59929.
https://doi.org/10.7554/eLife.59929

Share this article

https://doi.org/10.7554/eLife.59929

Further reading

    1. Evolutionary Biology
    Nagatoshi Machii, Ryo Hatashima ... Masato Nikaido
    Research Article

    Cichlid fishes inhabiting the East African Great Lakes, Victoria, Malawi, and Tanganyika, are textbook examples of parallel evolution, as they have acquired similar traits independently in each of the three lakes during the process of adaptive radiation. In particular, ‘hypertrophied lip’ has been highlighted as a prominent example of parallel evolution. However, the underlying molecular mechanisms remain poorly understood. In this study, we conducted an integrated comparative analysis between the hypertrophied and normal lips of cichlids across three lakes based on histology, proteomics, and transcriptomics. Histological and proteomic analyses revealed that the hypertrophied lips were characterized by enlargement of the proteoglycan-rich layer, in which versican and periostin proteins were abundant. Transcriptome analysis revealed that the expression of extracellular matrix-related genes, including collagens, glycoproteins, and proteoglycans, was higher in hypertrophied lips, regardless of their phylogenetic relationships. In addition, the genes in Wnt signaling pathway, which is involved in promoting proteoglycan expression, was highly expressed in both the juvenile and adult stages of hypertrophied lips. Our comprehensive analyses showed that hypertrophied lips of the three different phylogenetic origins can be explained by similar proteomic and transcriptomic profiles, which may provide important clues into the molecular mechanisms underlying phenotypic parallelisms in East African cichlids.

    1. Evolutionary Biology
    Julia D Sigwart, Yunlong Li ... Jin Sun
    Research Article

    A major question in animal evolution is how genotypic and phenotypic changes are related, and another is when and whether ancient gene order is conserved in living clades. Chitons, the molluscan class Polyplacophora, retain a body plan and general morphology apparently little changed since the Palaeozoic. We present a comparative analysis of five reference quality genomes, including four de novo assemblies, covering all major chiton clades, and an updated phylogeny for the phylum. We constructed 20 ancient molluscan linkage groups (MLGs) and show that these are relatively conserved in bivalve karyotypes, but in chitons they are subject to re-ordering, rearrangement, fusion, or partial duplication and vary even between congeneric species. The largest number of novel fusions is in the most plesiomorphic clade Lepidopleurida, and the chitonid Liolophura japonica has a partial genome duplication, extending the occurrence of large-scale gene duplication within Mollusca. The extreme and dynamic genome rearrangements in this class stands in contrast to most other animals, demonstrating that chitons have overcome evolutionary constraints acting on other animal groups. The apparently conservative phenome of chitons belies rapid and extensive changes in genome.