Identification and characterization of genes and regulatory elements under local natural selection in modern humans

The Out-of-Africa Model of Human Evolution postulates the origins of modern humans in East Africa and their subsequent spread across the entire globe roughly during the last 100,000 years. In manifold migrations, human populations were exposed to different environmental conditions, including climatic changes, uncommon diets as well as new diseases. From an evolutionary point of view this implies that local natural selection has contributed substantially to the present distribution of genetic diversity among humans. Only recently, five years after the decipherment of the human genome, the analysis of genetic polymorphism data from several major human populations has given a much clearer picture of the human genetic diversity and the human genome structure. This public data holds the promise to be key for evolutionary biologists in their search for signs of local positive selection in the human genome. A set of promising candidate genes and regulatory regions with conceivably locally selected associated traits, including skin differences and disease, has been filtered out and selected for further analysis. These and other candidate loci will be tested for signs of positive selection in an integrative approach in diverse set of worldwide human populations. After initial genotyping and population genetics tests for positive selection, both (disease/phenotype) association studies and possibly functional studies, e.g. promoter and mRNA expression analyses, are planned for some candidate loci. Ideally, such an approach integrating genetic diversity, function and associated phenotypic traits or diseases will help to identify strong cases for selection in modern humans.