A comprehensive international study has revealed striking similarities as well as some significant differences in the regulation of mouse and human genomes.
A series of papers published by the mouse ENCODE (ENCyclopedia Of DNA Elements) consortium shows that many regulatory sequences in humans do have counterparts in the mouse genome. However, the regulation of some key genes varies between mice and humans.
It was already known that most human genes coding for protein have closely related genes in mice, and this makes the mouse a useful model organism for studying human disease. However, these coding genes only make up a small percentage of the genome. The genome contains a much larger proportion of regulatory regions and differences between these regions in mice and humans account for many of the differences between the two species.
'There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans,' said Professor Bing Ren of the University of California at San Diego, a principal author on the study. 'The differences are not random. They are clustered along certain pathways such as in genes regulating the immune system.'
In one companion study published in PNAS, researchers compared gene regulation patterns from 15 different types of cells and tissues from mice and humans. They found that any two tissues in mice were more similar to each other than to the relevant human tissues. For example, mouse liver and mouse kidney show greater similarity in gene expression than do mouse liver and human liver.
Commenting on the results, study co-author Dr Michael Beer of Johns Hopkins University said that evolution had 'carefully preserved the regulatory sequences for the most fundamental core cell processes but has left the rest to change as each organism required'.
Taken together, the published data could help determine when the mouse is an appropriate model to study human disease.
'Now we know which genes have expression patterns conserved between mouse and humans. For biological processes using these genes, mouse is an excellent model for aspects of human biology', said Professor Ross Hardison of Pennsylvania State University, a senior author.
However, Hardison also noted that the opposite would also sometimes be true; the study may explain why for some diseases, the mouse is unsuitable as a model organism.
The ENCODE project is funded by the US National Institutes of Health. Its findings were reported in four key papers in Nature, as well as in companion papers in PNAS and Science.