title: Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee, and macaque brains.
abstract: Adenosine-to-inosine (A-to-I) substitutions are the most common type of RNA editing in mammals. A-to-I RNA editing is particularly widespread in the brain and is known to play important roles in neuronal functions. In this study we investigated RNA-editing changes during human brain development and maturation, as well as evolutionary conservation of RNA-editing patterns across primates. We used high-throughput transcriptome sequencing (RNA-seq) to quantify the RNA-editing levels and assess ontogenetic dynamics of RNA editing at more than 8000 previously annotated exonic A-to-I RNA-editing sites in two brain regions--prefrontal cortex and cerebellum--of humans, chimpanzees, and rhesus macaques. We observed substantial conservation of RNA-editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident, with 40% of the annotated editing sites studied showing divergent editing levels among the three species and 16.5% of sites displaying statistically significant human-specific editing patterns. Across lifespan, we observed an increase of the RNA-editing level with advanced age in both brain regions of all three primate species.
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Li
authors.forename: Hindrike
authors.initials: H
authors.lastname: Bammann
authors.forename: Mingshuang
authors.initials: M
authors.lastname: Li
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Phoebe Chen
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
mesh_terms: D000367:Age Factors; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D017393:RNA Editing; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D059467:Transcriptome
keywords: RNA editing; aging; brain; chimpanzee; evolution; human