Transcriptome innovations in primates revealed by single-molecule long-read sequencing

  1. Guojie Zhang9,10,11,12
  1. 1Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003 Barcelona, Spain;
  2. 2BGI-Shenzhen, Shenzhen 518083, China;
  3. 3Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain;
  4. 4Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;
  5. 5Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain;
  6. 6College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
  7. 7Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain;
  8. 8CNAG-CRG, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain;
  9. 9State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;
  10. 10Section for Ecology and Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen 2200, Denmark;
  11. 11Evolutionary and Organismal Biology Research Center, School of Medicine, Zhejiang University, Hangzhou 310058, China
  1. 12 These authors contributed equally to this work.

  • Corresponding authors: tomas.marques{at}upf.edu, david.juan{at}upf.edu, guojiezhang{at}zju.edu.cn
  • Abstract

    Transcriptomic diversity greatly contributes to the fundamentals of disease, lineage-specific biology, and environmental adaptation. However, much of the actual isoform repertoire contributing to shaping primate evolution remains unknown. Here, we combined deep long- and short-read sequencing complemented with mass spectrometry proteomics in a panel of lymphoblastoid cell lines (LCLs) from human, three other great apes, and rhesus macaque, producing the largest full-length isoform catalog in primates to date. Around half of the captured isoforms are not annotated in their reference genomes, significantly expanding the gene models in primates. Furthermore, our comparative analyses unveil hundreds of transcriptomic innovations and isoform usage changes related to immune function and immunological disorders. The confluence of these evolutionary innovations with signals of positive selection and their limited impact in the proteome points to changes in alternative splicing in genes involved in immune response as an important target of recent regulatory divergence in primates.

    Footnotes

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.276395.121.

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

    • Received November 16, 2021.
    • Accepted July 12, 2022.

    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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