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

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%), pinp...

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Autores principales: van der Lee, Robin, Wiel, Laurens, van Dam, Teunis J.P., Huynen, Martijn A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737536/
https://www.ncbi.nlm.nih.gov/pubmed/28977405
http://dx.doi.org/10.1093/nar/gkx704
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author van der Lee, Robin
Wiel, Laurens
van Dam, Teunis J.P.
Huynen, Martijn A.
author_facet van der Lee, Robin
Wiel, Laurens
van Dam, Teunis J.P.
Huynen, Martijn A.
author_sort van der Lee, Robin
collection PubMed
description 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.
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spelling pubmed-57375362018-01-09 Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts van der Lee, Robin Wiel, Laurens van Dam, Teunis J.P. Huynen, Martijn A. Nucleic Acids Res Genomics 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. Oxford University Press 2017-10-13 2017-08-11 /pmc/articles/PMC5737536/ /pubmed/28977405 http://dx.doi.org/10.1093/nar/gkx704 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genomics
van der Lee, Robin
Wiel, Laurens
van Dam, Teunis J.P.
Huynen, Martijn A.
Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title_full Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title_fullStr Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title_full_unstemmed Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title_short Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
title_sort genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737536/
https://www.ncbi.nlm.nih.gov/pubmed/28977405
http://dx.doi.org/10.1093/nar/gkx704
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