[Walid H. Gharib and Marc Robinson-Rechavi. When orthologs diverge between human and mouse. Brief Bioinform. 2011 Sep; 12(5): 436–441.]
Despite the common assumption that orthologs usually share the same function, there have been various reports of divergence between orthologs, even among species as close as mammals. The comparison of mouse and human is of special interest, because mouse is often used as a model organism to understand human biology. We review the literature on evidence for divergence between human and mouse orthologous genes, and discuss it in the context of biomedical research.
We believe that both small-scale and large-scale studies provide evidence that functional divergence between human and mouse orthologs, although a minority phenomenon, still affects a significant proportion of genes. Divergence of gene expression, of alternative splicing, and of mutant phenotypes, each affect of the order of 10–20% of ortholog pairs, under conservative estimates. If these and other different processes affect different genes, then it might be a majority of genes which are affected. But even if the same genes differ in expression pattern, splicing, etc., then having ~15% of human-mouse orthologs with strong differences will affect many pathways and biological processes of interest.