Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts

被引:49
作者
van der Lee, Robin [1 ,3 ]
Wiel, Laurens [1 ,2 ]
van Dam, Teunis J. P. [1 ,4 ]
Huynen, Martijn A. [1 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Ctr Mol & Biomol Informat, Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Human Genet, Nijmegen, Netherlands
[3] Univ British Columbia, Dept Med Genet, BC Childrens Hosp, Ctr Mol Med & Therapeut,Res Inst, Vancouver, BC, Canada
[4] Univ Utrecht, Fac Sci, Dept Biol, Theoret Biol & Bioinformat, Utrecht, Netherlands
关键词
MULTIPLE SEQUENCE ALIGNMENT; DECAY-ACCELERATING FACTOR; PHYLOGENETIC ANALYSIS; NATURAL-SELECTION; ADAPTATION; REVEALS; GENES; DATABASE; ANCIENT; IMPROVEMENTS;
D O I
10.1093/nar/gkx704
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cellmembrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associatedCENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus-human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are avail-able at https://github.com/robinvanderlee/positive-selection.
引用
收藏
页码:10634 / 10648
页数:15
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