The 84th Annual Meeting of the American Association of Physical Anthropologists (2015)

Analysis of cell-specific regulatory DNA reveals elevated immune specificity in genomic regions of high Neandertal ancestry


Department of Biological Statistics and Computational Biology, Cornell University

March 26, 2015 1:15, Lindbergh Add to calendar

Following King and Wilson, many studies have suggested the importance of regulatory evolution in driving adaptive divergence between species. This observation makes regulatory regions prime candidates for adaptive introgression between closely related populations. This is particularly true in the adaptive immune system, where genetic variation is essential to adaptive responses to pathogen diversity. Neandertals, a population of archaic humans that lived in Europe and Central Asia between ~200 and 30 thousand years ago make up at least 1.5% of the ancestry of modern humans with recent ancestry outside of sub-Saharan Africa. We tested the hypothesis that Neandertal introgression contributed disproportionately to the immune systems of modern humans. To that end, we analyzed regulatory specificity in a set of DNase I hypsersensitive sites, a genomic approach to characterize regulatory DNA, from karyotype normal immune- and non-immune cells from the ENCODE project. We find that DHS with higher amounts of Neandertal ancestry in the 1000 genomes project are enriched with regulatory regions that are highly specific to active T-cells. we further characterize these results in the context of natural selection by utilizing information about the haplotype structure around T-cell specific regulatory sites, information content of Neandertal-derived alleles in binding motifs, and gene-expression data.

This research was funded by the Cornell Center for Comparative and Population Genomics (3CPG).