Adaptive selection in human populations

Previous scans of positive selection have revealed hundreds of regions in our genome bearing the molecular signatures of hard selective sweeps. However, in very few cases the putative adaptive variants and phenotypes behind such signatures have been elucidated. The two main aims of the project will be first to detect, in a robust and reliable way, the existence of footprints of positive (adaptive) selection in the genome of several human populations and ape species; and second to understand the underlying biological bases by dissecting them in a broad biological and functional context. For that, we propose to (i) generate and compile full genome sequencing data in a number of great ape species including chimpanzees, bonobos, orangu-tans, and gorilla and in different human populations of special interest such as Africans, Gypsies, Philippinos and Papua New Guinea pygmies (negritos); (ii) improve and integrate state-of-the-art evolutionary methods to perform genome-wide scans of selection including specific tests for hard and soft sweeps; (iii) expand the 1000 Genomes Selection Browser (http://hsb.upf.edu) with the novel test statistics and composite scores to be generated in the new human populations included in the phase 3 of the 1000 Genomes project; (iv) analyze selection in the context of functional pathways and complex biological networks; (v) identify functional variation in the presumably adaptive regions by integrating signatures of selection with the latest functional element annotations in the human genome and the different in-silico functional predictions available; (vi) experimentally validate through cutting-edge molecular biology techniques the putatively adaptive variants identified and (vii) compile and/or perform relevant phenotype association studies. This combined integrative approach will provide fundamental insights into our understanding of the adaptive allelic variants and phenotypes resulting from the different environmental and ecological changes we experienced in our past. Furthermore, all the statistics and composite scores for selection obtained in the new compiled populations will be made publicly available for the research community through the 1000 Genomes Selection Browser (http://hsb.upf.edu).