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

  • 4,695
    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. Ecology
    2. Evolutionary Biology
    Vendula Bohlen Šlechtová, Tomáš Dvořák ... Joerg Bohlen
    Research Article

    Eurasia has undergone substantial tectonic, geological, and climatic changes throughout the Cenozoic, primarily associated with tectonic plate collisions and a global cooling trend. The evolution of present-day biodiversity unfolded in this dynamic environment, characterised by intricate interactions of abiotic factors. However, comprehensive, large-scale reconstructions illustrating the extent of these influences are lacking. We reconstructed the evolutionary history of the freshwater fish family Nemacheilidae across Eurasia and spanning most of the Cenozoic on the base of 471 specimens representing 279 species and 37 genera plus outgroup samples. Molecular phylogeny using six genes uncovered six major clades within the family, along with numerous unresolved taxonomic issues. Dating of cladogenetic events and ancestral range estimation traced the origin of Nemacheilidae to Indochina around 48 mya. Subsequently, one branch of Nemacheilidae colonised eastern, central, and northern Asia, as well as Europe, while another branch expanded into the Burmese region, the Indian subcontinent, the Near East, and northeast Africa. These expansions were facilitated by tectonic connections, favourable climatic conditions, and orogenic processes. Conversely, aridification emerged as the primary cause of extinction events. Our study marks the first comprehensive reconstruction of the evolution of Eurasian freshwater biodiversity on a continental scale and across deep geological time.

    1. Evolutionary Biology
    Ljiljana Mihajlovic, Bharat Ravi Iyengar ... Yolanda Schaerli
    Research Article

    Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.