Why Mouse Matters
Overall, mice and humans share virtually the same set of genes. Almost every gene found in one species so far has been found in a closely related form in the other. Of the approximately 4,000 genes that have been studied, less than 10 are found in one species but not in the other.
Both the mouse and human genomes contain about 3.1 billion base pairs (or chemical letters). Only about 5 percent of the sequence consist of protein-coding regions (genes). More than 90 percent of the genome is non-coding DNA, sometimes called "junk" DNA, that has no known function. Because of the vast amount of non-coding DNA, it is very hard to recognize the genes simply by looking at one sequence alone; even the best of today's computational programs fail to identify many coding sequences and misidentify others. It is similarly difficult to identify regulatory regions within DNA - the "switches" that turn gene expression on or off, up or down - as they exist only as poorly defined "consensus" sequences.
On average, the protein-coding regions of the mouse and human genomes are 85 percent identical; some genes are 99 percent identical while others are only 60 percent identical. These regions are evolutionarily conserved because they are required for function. In contrast, the non-coding regions are much less similar (only 50 percent or less). Therefore, when one compares the same DNA region from human and mouse, the functional elements clearly stand out because of their greater similarity. Scientists have developed computer software that automatically aligns human and mouse sequences making the protein-coding and regulatory regions obvious.
Human, mouse and other mammals shared a common ancestor approximately 80 million years ago. Therefore the genomes of all mammals are comparably similar. Comparisons of the DNA sequence of the dog or the cow with that of the human theoretically would be quite informative. However, the mouse has a major advantage in that it is a well-established experimental model. Not only can genes easily be found in mouse genome sequence, but it also is possible to test experimentally the function of those genes in the mouse. Thus, scientists can mimic in mice the effect of DNA alterations that occur in human diseases and carefully study the consequences of these DNA misspellings. Mouse models also afford the opportunity to test possible therapeutic agents and evaluate their precise effects.
