The mouse (Mus musculus) is our closest relative among model organism in genetics. Photo: George Shuklin.
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From bacteria to elephants, from flowers to humans, all living things follow instructions written in the universal language of DNA. All living things contain similar building blocks — proteins encoded by DNA. And all diseases can be traced back to malfunctioning genes or proteins.
The four model organisms — yeast, worm, fly, and mouse — share vast numbers of genes, proteins, and even genetic pathways with humans.
Yeast (Saccharomyces cerevisiae)
- A single, free-living cell, only 3 microns in diameter (4,000 of them lined up would measure an inch).
- Reproduces by budding and doubles every 90 minutes.
- Its genome was sequenced in 1996.
- 12 million base pairs of DNA.
- 6,000 genes, of which at least 31% have human equivalents.
Worm (Caenorhabditis elegans)
- A multicellular animal, 1 millimeter (0.04 inch) long.
- Lifespan: 2-3 weeks. A new generation every 3 days.
- Its genome was sequenced in 1998.
- 99 million base pairs of DNA.
- 19,099 genes, of which 40% have human equivalents.
Mouse (Mus musculus)
- Our closest relative among model organism, 120 millimeters (6.6 inches) long.
- Lifespan: 2 years. A new generation every 9 weeks.
- Its genome sequence is expected in 2001.
- An estimated 3 billion base pairs of DNA (as in humans).
- An estimated 40,000 genes (as in humans).
- Almost every human gene has a counterpart in the mouse, and some blocks of sequenced mouse DNA are proving impossible to tell apart from the human versions.
Fly (Drosophila melanogaster)
- A multicellular animal with complex behavior, 4 millimeters (0.16 inch) long.
- Lifespan: 3-4 months. A new generation every 10 days.
- Its genome was sequenced in March 2000.
- 165 million base pairs of DNA.
- 13,600 genes, of which about 50% have human equivalents.
Human (Homo sapiens)
- 5-6 feet tall.
- Lifespan: About 40 years in developing nations, 60-70 years in the United States and other industrial nations. A new generation every 20-25 years.
- The human genome was sequenced (preliminary draft) in June 2000.
- 3 billion base pairs of DNA.
- An estimated 40,000 genes.
Despite their obvious differences in size and way of life, all these model organisms make proteins that carry out the same core functions as in humans telling the organism when and how to grow, reproduce, fight of stresses, and eventually die.
Human disease genes that are found in flies, worms, and yeast
Flies don’t get kidney disease, and worms don’t get heart disease, yet many of the human genes that are faulty in these and other human disorders have parallel genes in model organisms, where they can be studied more easily.
After the fly’s genome was sequenced in March 2000, a team of scientists found that 61% of the human genes known to be mutated in 289 human diseases have close equivalents in flies. Many of these genes also have parallels in worms and even in yeast.
[Examples] of similarity between some of the human disease genes and genes that have been sequenced in flies, worms, and yeast is shown below.2 [Organisms whose genes exhibit] the highest degree of similarity are:
- Juvenile Parkinson Disease: fly
- Cancer of the Thyroid: fly
- Heredity deafness: fly, worm, yeast
- Leukemia: fly
- Cystic Fibrosis: fly, worm
- Wilson Disease (a liver disorder): fly, worm, yeast
- Hereditary Nonpolyposis Cancer (a colon disease): fly, worm, yeast
- Multiple Exostoses (a bone disorder): fly
- Familial Cardiac Myopathy (inherited cardiac disease): fly, worm, yeast
- Pancreatic Cancer: fly
- Duchenne Muscular Dystrophy: fly, worm
- Xeroderma Pigmentosum D (early-onset skin cancer): fly, yeast
Proteomics — a new approach to treatment of disease
To speed up the search for better treatments, some scientists now want to move on from genomics, the study of all the genes in an organism’s cells, to the next step — proteomics, the study of all the proteins specified by these genes and how the proteins interact.
Proteins are the body’s beams and rafters, movers and engineers, as well as message givers and infection fighters. But proteins don’t act alone — they bind to other proteins, affecting them. So when a mutant gene produces a defective protein, it can mess up whole chains of interactions with other proteins, causing disease.
To cure, then, might be to interrupt — or compensate for — some of the faulty interactions. But first these need to be precisely identified. This is where model organisms such as yeast and flies are proving particularly useful.
A decade ago, Stanley Fields, an HHMI investigator at the University of Washington, Seattle, devised an ingenious way to identify pairs of proteins that physically interact with one another. Now he and his collaborators are using this “two-hybrid” system to explore the protein interactions in yeast. The scientists recently identified 957 interactions involving 1,004 yeast proteins. Similar interactions are very likely to exist between corresponding proteins in humans.
Meanwhile, Stuart Schreiber and his colleagues at Harvard University have adapted Patrick Brown’s microarrays technique — originally devised for DNA — for use with proteins, enabling them to study more than 10,000 proteins simultaneously. In this way, they detected large numbers of previously unknown protein interactions. They also screened hundreds of small molecules to see which ones would interact with the proteins in the microarrays.
Both of these approaches are providing new leads for a wide array of potential new drugs, we well as laying the groundwork for a far more precise medical science.
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