1. Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
- Author
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van der Lee, Robin, Wiel, Laurens, van Dam, Teunis J P, Huynen, Martijn A, Sub Bioinformatics, Theoretical Biology and Bioinformatics, Sub Bioinformatics, and Theoretical Biology and Bioinformatics
- 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] - 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.
- Published
- 2017