Comparative transcriptomics of primary cells in vertebrates

  1. Michiel J.L. de Hoon2
  1. 1College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar;
  2. 2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan;
  3. 3Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom;
  4. 4MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom;
  5. 5The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark;
  6. 6RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama 230-0045, Japan;
  7. 7Telethon Kids Institute, University of Western Australia, Perth, WA 6009, Australia;
  8. 8RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako 351-0198, Japan;
  9. 9Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA;
  10. 10International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan;
  11. 11Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA 6009, Australia;
  12. 12Vascular Biology and Translational Research, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052 Australia
  • 14 Present address: RIKEN Center for Brain Science, Wako 351-0198, Japan

  • Corresponding author: michiel.dehoon{at}riken.jp
  • Abstract

    Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have diverged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that divergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.

    Footnotes

    • 13 After RIKEN's reorganization in 2018, the RIKEN Center for Life Science Technologies, Division of Genomic Technologies continued as part of the RIKEN Center for Integrative Medical Sciences.

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.255679.119.

    • Freely available online through the Genome Research Open Access option.

    • Received August 8, 2019.
    • Accepted June 9, 2020.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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