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

Genome Res. 2020 Feb;30(2):250-262. doi: 10.1101/gr.254904.119. Epub 2020 Jan 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • DNA Methylation / genetics*
  • Epigenesis, Genetic
  • Gene Expression / genetics*
  • Gene Expression Profiling
  • Genomics*
  • Humans
  • Macaca mulatta / genetics
  • Pan troglodytes / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Processing, Post-Translational / genetics
  • Selection, Genetic*
  • Species Specificity