By Kevin Davies
January 15, 2003 | Not long ago, in the late 1990s, scientists often remarked on the “Gene of the Week” syndrome, so fast was the pace of disease gene identification. Now, “Genome of the Week” would be more accurate.
At press conferences held last month in Washington, London, and elsewhere, scientists celebrated the publication in Nature of the second mammalian genome – the mouse, Mus musculus. According to the international team of authors, anchored by the Whitehead Institute’s Eric Lander, this singular achievement will “play a crucial role in our understanding of the human genome and thereby help lay the foundation for biomedicine in the twenty-first century.”
The bulk of the mouse work was performed by scientists from three of the five genome centers that sequenced the human genome two years ago: Whitehead, Washington University in St. Louis, and the Wellcome Sanger Institute in Cambridge, UK. The genome assembly was based on the sequence of some 41.4 DNA fragments from strain C57BL/6J, using a combination of the hierarchical (map-based) sequencing strategy and whole-genome shotgun sequencing (popularized by Celera Genomics), which the authors say worked particularly well for mouse.
The resulting assembly, covering about 96 percent of the mouse genome, consists of 2.5 billion bases, almost 15 percent fewer than the human genome. Roughly one out of every two bases has been substituted in the 75 million years since humans and mice last shared a common ancestor. The mouse gene tally strongly supports last year’s paltry estimate in humans of about 30,000 genes. Interestingly, only 1 percent of genes appear to be unique to either species.
“It's a major step forward in biomedical research,” enthuses Elizabeth Fisher, a neurogeneticist at University College, London. “It's massively speeded up the rate with which we can find disease genes in the mouse and ergo in humans.”
The power of mouse genetics has been evident for decades. Past covers of Nature, for example, have celebrated the sex reversal of transgenic mice (carrying the male Sry gene) and the discovery of the leptin gene in the obese strain.
Before the mouse genome was sequenced, Fisher recalls, it took a team of three researchers in her laboratory four years to uncover a gene for motor neuron degeneration, and the subsequent breeding of several hundred mice. By contrast, “a couple of my Ph.D students each recently identified a new disease gene in just over 12 months, needing less than 100 mouse samples. So we're cutting down on our use of animals with the sequence, and we're speeding up disease-gene discovery.”
Next up is the rat genome, the first iteration of which — Rat 1.0 — was recently released. The project began in 2001 to the tune of $60 million, and is scheduled to run for two years. Having the rat sequence “will be a quantum leap for us,” says Tim Aitman, a professor of genetics at Imperial College, London. “The rat has been used as a model for human disease for 50 years,” including hypertension, heart failure, diabetes, and toxicology.
Later this year, scientists also expect to complete the sequence of another moderately interesting mammal – Homo sapiens.