A comparison of gene expression and DNA methylation patterns across tissues and species

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...

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Bibliographic Details
Published in:Genome research 2020-02, Vol.30 (2), p.250-262
Main Authors: Blake, Lauren E, Roux, Julien, Hernando-Herraez, Irene, Banovich, Nicholas E, Perez, Raquel Garcia, Hsiao, Chiaowen Joyce, Eres, Ittai, Cuevas, Claudia, Marques-Bonet, Tomas, Gilad, Yoav
Format: Article
Language:English
Subjects:
Animals
Comparative analysis
Deoxyribonucleic acid
Design
Divergence
DNA
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic
Gene expression
Gene Expression - genetics
Gene Expression Profiling
Genomics
Humans
Kidneys
Macaca mulatta - genetics
Natural selection
Pan troglodytes - genetics
Promoter Regions, Genetic - genetics
Protein Processing, Post-Translational - genetics
Resource
Selection, Genetic
Species Specificity
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Summary: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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.254904.119