RNA editome in rhesus macaque shaped by purifying selection

PLoS Genet. 2014 Apr 10;10(4):e1004274. doi: 10.1371/journal.pgen.1004274. eCollection 2014 Apr.


Understanding of the RNA editing process has been broadened considerably by the next generation sequencing technology; however, several issues regarding this regulatory step remain unresolved--the strategies to accurately delineate the editome, the mechanism by which its profile is maintained, and its evolutionary and functional relevance. Here we report an accurate and quantitative profile of the RNA editome for rhesus macaque, a close relative of human. By combining genome and transcriptome sequencing of multiple tissues from the same animal, we identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We verified 96.6% of editing sites in coding regions and 97.5% of randomly selected sites in non-coding regions, as well as the corresponding levels of editing by multiple independent means, demonstrating the feasibility of our experimental paradigm. Several lines of evidence supported the notion that the adenosine deamination is associated with the macaque editome--A-to-G editing sites were flanked by sequences with the attributes of ADAR substrates, and both the sequence context and the expression profile of ADARs are relevant factors in determining the quantitative variance of RNA editing across different sites and tissue types. In support of the functional relevance of some of these editing sites, substitution valley of decreased divergence was detected around the editing site, suggesting the evolutionary constraint in maintaining some of these editing substrates with their double-stranded structure. These findings thus complement the "continuous probing" model that postulates tinkering-based origination of a small proportion of functional editing sites. In conclusion, the macaque editome reported here highlights RNA editing as a widespread functional regulation in primate evolution, and provides an informative framework for further understanding RNA editing in human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Adenosine Deaminase / genetics
  • Animals
  • Genome / genetics
  • Macaca mulatta / genetics*
  • RNA / genetics*
  • RNA Editing / genetics*
  • Transcriptome / genetics


  • RNA
  • Adenosine Deaminase
  • Adenosine

Grants and funding

This work was supported by grants from the National Key Basic Research Program of China (http://www.973.gov.cn/English/Index.aspx) [2013CB531202, 2012CB518004], Beijing Joint Research Program of Scientific Research and Graduate Student Training (http://www.bjedu.gov.cn) and the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) [31171269, 31221002]. BC-MT is supported by National Science Council (http://web1.nsc.gov.tw/) [NSC102-2321-B-182-007] and National Health Research Institute (http://www.nhri.org.tw/) [NHRI-EX103-10321SI]. ZP is supported by the Guangzhou Key Laboratory of Cancer, Trans-Omics Research in BGI-Guangzhou. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.