Mouse models of human evolution

The genotype-phenotype map of human evolution is difficult to access since humans cannot be crossed with other species. Most of the ∼20 million genetic changes that occurred since the human and the chimpanzee lineage split, are fixed and hence completely correlated with all phenotypic changes that occurred during human evolution. While patterns of selection and functional information on genomic regions are crucial to prioritize on particular genetic changes, experimental access is needed to test the resulting genotype-phenotype hypotheses and to better understand their mechanisms. The validity and the practicability of such functional assays might be the major limiting factors for understanding human evolution on a functional genetic level. While the mouse as a system for modeling human diseases is well established, it has only more recently been used to study aspects of human evolution, revealing first insights into the evolution of regulatory elements, synapse densities, brain size or speech. Together with a mouse model of a recent, still polymorphic human change, these studies allow careful optimism that at least some aspects of human evolution can be functionally studied in mice.