Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Signatures of archaic adaptive introgression in present-day human populations (#307)

Fernando Racimo 1 , David Gokhman 2 , Matteo Fumagalli 3 , Davide Marnetto 4 , Torben Hansen 5 , Ida Moltke 6 , Anders Albrechtsen 6 , Liran Carmel 2 , Emilia Huerta-Sánchez 7 , Rasmus Nielsen 1 8
  1. Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States
  2. Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel
  3. Department of Genetics, Evolution, and Environment, University College London, London, UK
  4. Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy
  5. The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  6. The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  7. School of Natural Sciences, University of California Merced, Merced, California, United States
  8. Department of Statistics, University of California Berkeley, Berkeley, California, United States

Comparisons of DNA from archaic and modern humans show that these groups interbred, and in some cases received an evolutionary advantage from doing so – a process known as adaptive introgression (AI). However, introgression by itself changes both the haplotype structure and the distribution of allele frequencies in a genomic region, thus confounding traditional tests for detecting positive selection that do not model introgression. Here we explore models involving both introgression and positive selection to investigate the behavior of various statistics under AI. We find that the number and allelic frequencies of sites that are uniquely shared between archaic humans and specific present-day populations are particularly useful for detecting AI. We then examine the 1000 Genomes dataset to characterize the landscape of uniquely shared archaic alleles in human populations. Finally, we identify regions that were likely subject to adaptive introgression and discuss some of the most promising candidate genes located in these regions. One of these is the TBX15/WARS2 region, which has been previously found to be under positive selection in Greenlandic Inuit and has also been associated with body fat distribution in humans. We show that an archaic haplotype was likely introduced into Eurasians by a population closely related to Denisovans, and was then subject to positive selection in a much larger geographic region than just Greenland. Furthermore, the introgressed SNPs are associated with changes in expression and methylation patterns of WARS2 and TBX15 in multiple tissues, suggesting the introgressed haplotype may have altered regulatory patterns in the region. Our study helps to elucidate the landscape of adaptive events possible through introgression from archaic hominids. It also helps us understand the consequences of these events on the phenotypic make-up of modern humans as they expanded around the globe.