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

• Published in: RNA (Cambridge) Vol. 24; no. 4; pp. 585 - 596
• Main Authors: Mazin, Pavel V, Jiang, Xi, Fu, Ning, Han, Dingding, Guo, Meng, Gelfand, Mikhail S, Khaitovich, Philipp
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.04.2018
• Subjects: Age; Alternative Splicing - genetics; Animals; Evolution, Molecular; Evolutionary conservation; Exons; Gene regulation; Humans; Macaca mulatta - embryology; Macaca mulatta - genetics; Pan troglodytes - embryology; Pan troglodytes - genetics; Prefrontal cortex; Prefrontal Cortex - embryology; Protein Isoforms - genetics; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA-binding protein; Species; Splicing; brain development; transcriptomics; RNA-seq; alternative splicing
• ISSN: 1355-8382; 1469-9001
• DOI: 10.1261/rna.064931.117

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 -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.