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Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans

View ORCID ProfileAaron J. Sams, Anne Dumaine, Yohann Nédélec, Vania Yotova, Caroline Alfieri, Jerome E. Tanner, Philipp W. Messer, Luis B. Barreiro
doi: https://doi.org/10.1101/051466
Aaron J. Sams
1Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY
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  • For correspondence: as2847@cornell.edu messer@cornell.edu luis.barreiro@umontreal.ca
Anne Dumaine
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
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Yohann Nédélec
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
3Department of Biochemistry, University of Montreal, Montreal, Qc, Canada
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Vania Yotova
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
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Caroline Alfieri
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
4Department of Microbiology and Immunology, University of Montreal, Montreal, Qc, Canada
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Jerome E. Tanner
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
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Philipp W. Messer
1Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY
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  • For correspondence: as2847@cornell.edu messer@cornell.edu luis.barreiro@umontreal.ca
Luis B. Barreiro
2Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada
5Department of Pediatrics, University of Montreal, Montreal, Qc, Canada
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  • For correspondence: as2847@cornell.edu messer@cornell.edu luis.barreiro@umontreal.ca
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Abstract

The 2’-5’ oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations; yet, strong evidence of positive selection in the OAS region is still lacking. Here we used a combination of neutral coalescent simulations and neutrality tests to firmly demonstrate a signal of adaptive introgression at the OAS locus. Furthermore, we characterized the functional consequences of the Neandertal haplotype in the transcriptional regulation of OAS genes at baseline and infected conditions. We found that cells from people with the Neandertal-like haplotype express lower levels of OAS3 upon infection, as well as distinct isoforms of OAS1 and OAS2. Notably, the Neandertal-introgressed haplotype reintroduced an ancestral splice variant of OAS1 encoding a more active protein, suggesting that adaptive introgression occurred as a means to resurrect adaptive variation that had been lost outside Africa.

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  • ↵†† These authors jointly supervised this work

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Posted May 04, 2016.
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Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans
Aaron J. Sams, Anne Dumaine, Yohann Nédélec, Vania Yotova, Caroline Alfieri, Jerome E. Tanner, Philipp W. Messer, Luis B. Barreiro
bioRxiv 051466; doi: https://doi.org/10.1101/051466
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Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans
Aaron J. Sams, Anne Dumaine, Yohann Nédélec, Vania Yotova, Caroline Alfieri, Jerome E. Tanner, Philipp W. Messer, Luis B. Barreiro
bioRxiv 051466; doi: https://doi.org/10.1101/051466

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