Of Mice and Men: We’re Quite Similar, Genetically

It has been squeaking around us for millenniums, reviled as a disease-spreading pest or cherished as a collector’s curiosity and a powerful scientific tool.

Now, the common laboratory mouse, Mus musculus, has scurried out of its hole to show us what it’s made of. An international consortium of scientists announced today in the journal Nature that it has completed a sophisticated draft of the mouse genome, and has published the first detailed comparison of the genetic codes of mouse and man.

Scientists heralded the advance as every bit as important, if not more, as the decoding of the human genome because of the mouse’s critical role in biomedical research.

As it turns out, mice and humans aren’t that different. Both species have about 30,000 genes, although the full mouse genome is about 15% smaller. Very few of the genes -- less than 1% -- are unique to either species. Humans even possess the same set of mouse genes that direct the formation of a tail.

The mouse genome adds an important set of data to the human genome and the genomes of other key research species, such as yeast, fruit flies and roundworms.

Scientists say it will ease the ability to tackle medically important or just plain fascinating questions such as how bodies are built, how they decay and die, how diseases are caused, and how to prevent or cure them.

The advance is also crucial because having a blueprint from another mammal helps scientists extract meaning from the human genome’s vast code. By directly comparing these two genomes, scientists can deduce which parts are important and which are seemingly useless filler that can mutate and change at will.

“Having sequenced the human genome is all well and good,” said Eric Lander, director of the Whitehead/MIT Center for Genome Research, one of the institutes that sequenced the mouse genome.

But “the mouse provides us for the first time with the ability to turn the spotlight on what matters, and what probably doesn’t matter, in the human genome.”

The sequencing of the mouse genome was conducted by scientists of the Mouse Genome Sequencing Consortium at the Whitehead/MIT Institute, Washington University in St. Louis, and the Wellcome Trust Sanger Institute and the European Bioinformatics Institute in Hinxton, England. Researchers from 21 institutes around the world contributed to the analysis published today. The draft sequence covers 96% of the genome. Full completion is expected in the next few years.

A private company, Celera Genomics, has offered a different mouse genome sequence for a fee since 2001. But the availability now of a free version that can be accessed on the Web is a treasure trove for research, scientists say.

They have learned much already.

The mouse genome has helped scientists identify 1,200 new human genes -- and 9,000 new mouse genes. While the genes -- the key strings of DNA that direct the formation and functioning of organisms -- are largely the same in both species, the mouse has expanded numbers of certain types, particularly those that are involved with smell, reproduction and processing certain toxins.

Scientists have also found that mouse and human genes tend to line up in a similar order, although chromosomes have broken and rejoined in all kinds of new patterns over the course of our separate evolutions.

Scientists are particularly enthralled by the finding that far more than just the genes appear to be closely conserved between mouse and human. The actual genes make up only 1.5% of the genome: the rest consists of DNA that may be unimportant, involved in turning the genes on and off or serving some other function.

But fully 5% of the genome has been closely preserved for 75 million years, the time when mouse and human split off from their last common ancestor. This percentage of preserved genetic information suggests that far more than just the genes are important.

Mice have long lived around human beings, and odd types with exotic fur, small size or the tendency to “waltz” in circles were bred and prized in Asia for centuries.

In Europe, “fancy” mouse breeding and collecting spawned a “National Mouse Club” in Victorian England.

In the early 20th century, Harvard University scientist William Castle saw that mice also could be eminently useful in the new-fangled science of genetics.

Mouse science blossomed, and thousands of different strains of mice are now studied. Scientists can delete or add genes to mice at will, and thus figure out their function. Stem-cell science, with its medical promise, got its start in mice. Mice have helped our understanding of many human maladies, from obesity and heart defects to hearing loss and cancer.

“Mice have taught us most of what we know about disease,” said Jake Lusis, a UCLA professor of human genetics and microbiology who uses mice to study heart disease and diabetes.

With the genome in hand, such findings are expected to come at a much faster pace.

For example, in two papers accompanying today’s release, scientists used the mouse genome to probe the genes connected with Down syndrome, in which a baby is born with an extra chromosome 21. They surveyed all the known genes on the mouse equivalent to that chromosome to see how each one acted during mouse development. They found genes that are active in the developing brain or heart at crucial times, and thus might be key in the mental retardation and heart abnormalities common with Down syndrome.

The mouse-human comparison may also help illuminate the very process of evolution. Scientists don’t yet understand what kinds of genetic changes occur when creatures diverge from each other and form new species with different bodies, behaviors and habits.

They are intrigued by the fact that at least half of the mouse and human genomes are wildly different from each other, stuffed with odd DNA elements that hop from place to place in the genome, leaving copies of themselves behind. For unknown reasons, there is a lot more jumping going on in the mouse.

The structure of the mouse genome is also evolving twice as fast as the human genome. But the rates of change are very different from one site in the genome to the next, a surprising finding that may overturn the previous conception of a uniform pace of mutation.

“The greatest fear we had was we’d look at the mouse and human genomes and we’d say, ‘Well, that’s kind of what we thought,’ ” said Dr. Francis Collins, director of the National Human Genome Research Institute, a major funder of the mouse genome effort. “We need not have feared.”

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Mice, men and bacteria

The sequencing and analysis of the mouse genome provides scientists with the basic genetic information on one of the most important laboratory research organisms. So far, scientists have sequenced the genomes of about 15 plants, fungi and animals, as well as hundreds of bacteria and viruses. Some of the most significant are:

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Name: Saccharomyces cerevisiae (yeast)

Number of genes: 5,600

Scientific publication date: 1997

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Name: Escherichia coli (bacterium)

Number of genes: 4,800

Scientific publication date: 1997

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Name: Caenorhabditis elegans (nematode worm)

Number of genes: 18,300

Scientific publication date: 1998

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Name: Drosophila melanogaster (fruit fly)

Number of genes: 13,600

Scientific publication date: 2000

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Name: Arabidopsis thaliana (mustard plant)

Number of genes: 25,700

Scientific publication date: 2000

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Name: Homo sapiens (human)

Number of genes: approx. 30,000

Scientific publication date: 2001+

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Name: Oryza sativa (rice)

Number of genes: 50,000

Scientific publication date: 2002

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Name: Mus musculus (lab mouse)

Number of genes: approx. 30,000

Scientific publication date: 2002

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+First draft of human genome was publicly announced in 2000

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Source: National Human Genome Research Institute