A comparison of gene expression and DNA methylation patterns across tissues and species
- Lauren E. Blake1,9,
- Julien Roux1,2,3,9,
- Irene Hernando-Herraez4,
- Nicholas E. Banovich1,
- Raquel Garcia Perez4,
- Chiaowen Joyce Hsiao1,
- Ittai Eres1,
- Claudia Cuevas1,
- Tomas Marques-Bonet4,5,6,7 and
- Yoav Gilad1,8
- 1Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA;
- 2Department of Biomedicine, University of Basel, 4031 Basel, Switzerland;
- 3Swiss Institute of Bioinformatics, 4031 Basel, Switzerland;
- 4Universitat Pompeu Fabra, Institute of Evolutionary Biology, 88 08003 Barcelona, Spain;
- 5Passeig de Lluís Companys, Catalan Institution of Research and Advanced Studies, 23 08010 Barcelona, Spain;
- 6Barcelona Institute of Science and Technology, Centre for Genomic Regulation, 88 08003 Barcelona, Spain;
- 7Universitat Autònoma de Barcelona, Institut Català de Paleontologia Miquel Crusafont, 08193 Barcelona, Spain;
- 8Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
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↵9 These authors contributed equally to this work.
Abstract
Previously published comparative functional genomic data sets from primates using frozen tissue samples, including many data sets from our own group, were often collected and analyzed using nonoptimal study designs and analysis approaches. In addition, when samples from multiple tissues were studied in a comparative framework, individuals and tissues were confounded. We designed a multitissue comparative study of gene expression and DNA methylation in primates that minimizes confounding effects by using a balanced design with respect to species, tissues, and individuals. We also developed a comparative analysis pipeline that minimizes biases attributable to sequence divergence. Thus, we present the most comprehensive catalog of similarities and differences in gene expression and DNA methylation levels between livers, kidneys, hearts, and lungs, in humans, chimpanzees, and rhesus macaques. We estimate that overall, interspecies and inter-tissue differences in gene expression levels can only modestly be accounted for by corresponding differences in promoter DNA methylation. However, the expression pattern of genes with conserved inter-tissue expression differences can be explained by corresponding interspecies methylation changes more often. Finally, we show that genes whose tissue-specific regulatory patterns are consistent with the action of natural selection are highly connected in both gene regulatory and protein–protein interaction networks.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.254904.119.
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Freely available online through the Genome Research Open Access option.
- Received July 18, 2019.
- Accepted January 2, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
