The biological basis of the unique human features separating us from even our closest relatives, the chimpanzee, constitutes one of the most fascinating problems in biological research. Based on the sequence of the human genome, the recently completed finished sequence of chimpanzee chromosome 22, the recently released draft sequence of the chimpanzee genome, as well as additional gene sequences in other primates (e.g. Clark et. al. 2003), we plan to identify likely candidates for playing an essential role in the molecular basis of these differences. This will particularly include genes with potentially novel functions in man, formed by fusion events between pre-existing genes or pre-existing genes with repetitive elements, genes showing accelerated evolution in the human lineage, with appropriate expression patterns (or human specific changes in expression patterns), and appropriate molecular or cellular function, as well as the orthologs of genes identified as being involved in cognition differences in the mouse. Candidate genes selected by this process will be analysed by evolutionary shadowing of their promoters, as well as, in some cases, coding and other regulatory regions, by in-situ hybridization of mouse orthologues in the postnatal mouse brain, and where appropriate, by in-situ hybridization in the brains of selected primates, complemented by a range of other techniques available at the different centres. Moreover, selected candidate genes for higher cognitive capabilities will be studied in vivo in the common marmoset monkey. Data generated within this project will be made available to collaborating groups in a special project data base, analogous to genome-matrix (www.genome-matrix.org), a common functional genomics database developed jointly by the MPI-MG and the resource centre of the German genome project (RZPD).