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

Genome Biology
Aaron J SamsLuis B Barreiro

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 broad array of selection tests in concert with neutral coalescent simulations to 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. We present evidence that a Neandertal haplotype at the OAS locus was subjected to positive selection in the human population. This haplotype is significantly associated with functional consequences at the level of transcriptional regulation of innate immune responses. Notably, we suggest that the Neandertal-introgressed haplotype likely reintroduced an ancestral splice variant of OAS1 encoding a more active protein, suggesting that adaptive introgression occurred as ...Continue Reading

References

Mar 30, 2017·The Journal of Experimental Medicine·Hélène Quach, Lluis Quintana-Murci
Feb 1, 2017·Genome Biology·Mark I McCarthy, Daniel G MacArthur
Apr 4, 2017·Genome Biology·Michael DannemannJanet Kelso
Apr 1, 2018·Molecular Ecology·Matthias SteinrückenYun S Song
Sep 20, 2018·Médecine sciences : M/S·Philippe CharlierJacques Hassin
Oct 29, 2018·The New Phytologist·Garrett M JanzenMatthew B Hufford
Feb 21, 2018·Nature Ecology & Evolution·Kelsey Elizabeth Johnson, Benjamin F Voight
Sep 12, 2017·Nature Reviews. Genetics·Stephanie Marciniak, George H Perry
Jan 15, 2020·Molecular Biology and Evolution·Alexandre Gouy, Laurent Excoffier
Jul 29, 2020·Nature Ecology & Evolution·David C RinkerJohn A Capra
Dec 5, 2017·Current Genetic Medicine Reports·Marianna Orlova, Erwin Schurr
Jul 31, 2018·Genome Biology·Fernando A SeixasJosé Melo-Ferreira
Jul 31, 2019·Nature Ecology & Evolution·Genelle F HarrisonLuis B Barreiro
Feb 19, 2019·Frontiers in Plant Science·Concetta BurgarellaCécile Berthouly-Salazar
Apr 15, 2020·Human Genetics·Luis B Barreiro, Lluis Quintana-Murci
Jun 20, 2020·PLoS Genetics·Derek SetterJoachim Hermisson
Apr 13, 2019·Nature Communications·Maxime RotivalLluis Quintana-Murci
Jan 4, 2020·Genome Biology·Maxime Rotival, Lluis Quintana-Murci

Citations

Jun 12, 1998·Pharmacology & Therapeutics·M R Player, P F Torrence
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Nov 26, 2008·Genome Research·Gary K ChenJeffrey D Wall
Aug 4, 2009·Genome Research·David H AlexanderKenneth Lange
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jean-Jacques Hublin
Dec 3, 2009·Nature Reviews. Genetics·Luis B Barreiro, Lluis Quintana-Murci
May 8, 2010·Science·Richard E GreenSvante Pääbo
May 14, 2011·Molecular Ecology Resources·Laurent Excoffier, Heidi E L Lischer
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Simon GravelCarlos D Bustamante
Sep 22, 2011·PloS One·Abigail W BighamMichael Bamshad
Feb 10, 2012·Molecular Biology and Evolution·Fernando L MendezMichael Hammer
Apr 20, 2012·Molecular Biology and Evolution·Melinda A YangMontgomery Slatkin
May 19, 2012·Science·Jacob A TennessenNHLBI Exome Sequencing Project
Aug 14, 2012·American Journal of Human Genetics·Fernando L MendezMichael Hammer
Sep 1, 2012·Science·Matthias MeyerSvante Pääbo
Jan 15, 2013·Molecular Biology and Evolution·Fernando L MendezMichael Hammer
May 17, 2013·Nature·Linfeng WuMichael Snyder
Dec 20, 2013·Nature·Kay PrüferSvante Pääbo
Jan 31, 2014·Science·Benjamin Vernot, Joshua M Akey
Jan 31, 2014·Nature·Sriram SankararamanDavid Reich
Feb 21, 2014·Molecular Biology and Evolution·Anna Ferrer-AdmetllaRasmus Nielsen
Jul 22, 2014·Nature·Emilia Huerta-SánchezRasmus Nielsen
Sep 6, 2014·Current Opinion in Immunology·Laure Ségurel, Lluis Quintana-Murci
Feb 17, 2015·American Journal of Human Genetics·Benjamin Vernot, Joshua M Akey
Mar 10, 2015·Nature Reviews. Microbiology·Doris L LaRockSamuel I Miller
May 13, 2015·Nature Reviews. Genetics·Fernando RacimoEmilia Huerta-Sánchez
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Eva Kille SawyerJon H Kaas
Aug 8, 2015·Molecular Biology and Evolution·Colin A MacleanJames G D Prendergast
Oct 4, 2015·Nature·1000 Genomes Project ConsortiumGonçalo R Abecasis
Nov 22, 2015·Molecular Ecology·Florencia SchlampPhilipp W Messer
Nov 25, 2015·Nature·Iain MathiesonDavid Reich
Jan 11, 2016·American Journal of Human Genetics·Matthieu DeschampsLluis Quintana-Murci
Apr 2, 2016·Current Biology : CB·Sriram SankararamanDavid Reich
Oct 21, 2016·Molecular Biology and Evolution·Fernando RacimoEmilia Huerta-Sánchez

Related Concepts

Real-Time Polymerase Chain Reaction
Immune Response
Transcriptional Regulation
Virus Diseases
Genome
Genes
Tract
Enzymes, antithrombotic
Gentamicins
Human Herpesvirus 2

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