Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques

Pavel V. Mazin, Xi Jiang, Ning Fu, Dingding Han, Meng Guo, Mikhail S. Gelfand, Philipp Khaitovich

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    Changes in splicing are known to affect the function and regulation of genes. We analyzed splicing events that take place during the postnatal development of the prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data obtained from 168 individuals. Our study revealed that among the 38,822 quantified alternative exons, 15% are differentially spliced among species, and more than 6% splice differently at different ages. Mutations in splicing acceptor and/or donor sites might explain more than 14% of all splicing differences among species and up to 64% of high-amplitude differences. A reconstructed trans-regulatory network containing 21 RNA-binding proteins explains a further 4% of splicing variations within species. While most age-dependent splicing patterns are conserved among the three species, developmental changes in intron retention are substantially more pronounced in humans.

    Original languageEnglish
    Pages (from-to)585-596
    Number of pages12
    JournalRNA
    Volume24
    Issue number4
    DOIs
    Publication statusPublished - Apr 2018

    Keywords

    • Alternative splicing
    • Brain development
    • RNA-seq
    • Transcriptomics

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