1Department of Biological Statistics and Computational Biology, Cornell University, 2Department of Genetics, CHU Sainte-Justine Research Center, 3Department of Biochemistry, University of Montreal, 4Department of Pediatrics, University of Montreal
April 14, 2016 3:00, Imperial Ballroom B
It is now clear the ancestry of all individuals living outside of sub-Saharan Africa is composed of roughly two percent Neandertal ancestry. Yet, it remains largely unclear to what extent this contribution from Neandertals impacts modern human biology, and further, to what extent it may have provided adaptive genetic variation to modern human populations. The immune system is one physiological system that harbors higher than typical amounts of genetic variation in order to provide a flexible set of responses to infection. Here we use coalescent simulation and population genetic approaches to demonstrate a signal of adaptive introgression in the 2'-5' oligoadenylate synthetase (OAS) gene cluster region of chromosome 12. The adaptive region encodes for three active OAS enzymes (OAS1-3) that are involved in the innate immune response to viral infection. In order to evaluate the functional consequences of the adaptive haplotype we infected primary macrophages and peripheral blood mononuclear cells from people with and without the Neandertal haplotype with a panel of viruses and viral-syntetic ligands. Our results show that people with the Neandertal-like haplotype show marked functional differences in the transcriptional regulation of OAS1 and OAS3 in response to virtually all viral agents tested, which illuminate the phenotypic effects of Neandertal haplotypes into the regulation of innate immune responses in modern human populations.