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Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
- Source :
- Nucleic Acids Research, 45(18), 10634. Oxford University Press, Nucleic Acids Research, gkx704, pp. 10634-10648, Nucleic Acids Research, gkx704, 10634-10648, Nucleic Acids Research
- Publication Year :
- 2017
-
Abstract
- 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 cell membrane 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-associated CENPO, 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 available at https://github.com/robinvanderlee/positive-selection.
- Subjects :
- 0301 basic medicine
Primates
Genome evolution
Evolution
Gene Conversion
Genomics
Computational biology
Major histocompatibility complex
Genome
Evolution, Molecular
03 medical and health sciences
Viral Proteins
Genetic
Receptors
Genetics
Journal Article
Animals
Humans
Selection, Genetic
GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Gene
Selection
Selection (genetic algorithm)
biology
Immunity
Molecular
Genetic Variation
Proteins
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Acquired immune system
Phenotype
Virus
030104 developmental biology
Virus Diseases
Multigene Family
Host-Pathogen Interactions
biology.protein
Receptors, Virus
Artifacts
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Subjects
Details
- Language :
- English
- ISSN :
- 03051048
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research, 45(18), 10634. Oxford University Press, Nucleic Acids Research, gkx704, pp. 10634-10648, Nucleic Acids Research, gkx704, 10634-10648, Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....dba36e4f5cd533b14534588ca9944b5a