RNA editome in rhesus macaque shaped by purifying selection.
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.
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Jia-Yu
JY
Chen
BGI-Guangzhou, Guangzhou, China; BGI-Shenzhen, Shenzhen, China.
Zhiyu
Z
Peng
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Rongli
R
Zhang
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Xin-Zhuang
XZ
Yang
Department of Biomedical Sciences and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Bertrand Chin-Ming
BC
Tan
School of Mathematical Sciences and Center for Quantitative Biology, Peking University, Beijing, China.
Huaying
H
Fang
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Chu-Jun
CJ
Liu
BGI-Shenzhen, Shenzhen, China.
Mingming
M
Shi
Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China.
Zhi-Qiang
ZQ
Ye
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Yong E
YE
Zhang
School of Mathematical Sciences and Center for Quantitative Biology, Peking University, Beijing, China.
Minghua
M
Deng
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Xiuqin
X
Zhang
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Chuan-Yun
CY
Li
D000241:Adenosine / Q000235:genetics; D000243:Adenosine Deaminase / Q000235:genetics; D000818:Animals; D016678:Genome / Q000235:genetics; D008253:Macaca mulatta / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
D012313:RNA; D000243:Adenosine Deaminase; D000241:Adenosine