title: Archaic Adaptive Introgression in TBX15/WARS2.
abstract: A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using single nucleotide polymorphism chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15.
authors.affiliation: Department of Integrative Biology, University of California Berkeley, Berkeley, CA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Racimo
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gokhman
authors.affiliation: Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: Department of Integrative Biology, University of California Berkeley, Berkeley, CA.
authors.forename: Amy
authors.initials: A
authors.lastname: Ko
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Moltke
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Carmel
authors.affiliation: School of Natural Sciences, University of California Merced, Merced, CA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sánchez
authors.affiliation: Department of Integrative Biology, University of California Berkeley, Berkeley, CA.|Department of Statistics, University of California Berkeley, Berkeley, CA.|Museum of Natural History, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000273:Adipose Tissue / Q000502:physiology; D000483:Alleles; D000818:Animals; D019175:DNA Methylation; D000072441:DNA, Ancient; D006116:Greenland; D006239:Haplotypes; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008957:Models, Genetic; D059125:Neanderthals; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D000072441:DNA, Ancient; D020825:T-Box Domain Proteins; C523795:TBX15 protein, human
keywords: Denisova; Native Americans; adaptive introgression; admixture.; methylation; positive selection