Genetic divergence between mouse and humans: a useful direction for gene pathway analysis

Preliminary results in comparative genetics have revealed a growing list of differences between mice and humans (Strachan et al. [1997]: Nat. Genet. 16:126-132). However, it is increasingly apparent that some of these differences are not accompanied by changes in function. Such differences are nevertheless useful because they represent a sort of genetic experiment that provides evidence helpful in deducing how the genetic circuits work. This article draws attention to some recent results. First, we briefly report on representative examples of genetic differences between rodents and humans, suggesting, as expected, that such divergence is abundant and diverse at all levels of gene regulation. Second, on the basis of a more detailed analysis bearing on four examples, we emphasize that the study of genetic differences associated with little or no functional divergence is likely to be a profitable direction for future analysis of genetic pathways. Finally, we suggest that apparently nonfunctional genetic divergence may underlie different susceptibilities to disease. A detailed knowledge of human-mouse genetic divergence will provide an indispensable framework for extrapolating the molecular effects of mutations and teratogens from mice to humans in studies of abnormal development.