articlehighlights

Mapping the genome of different species reveals that:

• all living things share parallel genes
• the genome of other species can be used for human disease research
• many diseases are caused by defective genes or proteins
• so far, the mouse offers the best insight into human disease

June 2001

The mouse (Mus musculus) is our closest relative among model organism in genetics. Photo: George Shuklin.

Note: Because some of the information in this article may be outdated, it has been archived.

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.

© 2001, American Institute of Biological Sciences. Educators have permission to reprint articles for classroom use; other users, please contact editor@actionbioscience.org for reprint permission. See reprint policy.

Species: Comparing Their Genome

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Howard Hughes Medical Institute

Discover the research and medical breakthroughs at HHMI. The section for young scientists has interesting and fun activities and information.
http://www.hhmi.org/

The Human Genome Project

Find out about the work of this worldwide project, led by the U.S., to sequence the entire human genome. The site includes sections on education, medicine, and ethical issues.
http://www.ornl.gov/TechResources/Human_Genome/

A User’s Guide to the Human Genome

Nature Geneticsmagazine provides an overview of the types of data available, details on how these data can be browsed, and step-by-step instructions and strategies for using many of the most commonly used tools for sequence-based discovery.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v32/n1s/index.html

From proteins to proteomics

An excellent synopsis, although somewhat technical, of proteomics and how it can revolutionize drug development for human diseases.
http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/proteomics.page

For teachers: Natural diversity lesson units

The Arkansas Natural Heritage Commission has created a 5-unit classroom resource with lesson plans per unit suitable for different grade levels, from grades 4 to 12. Each lesson is a pdf file.
http://www.naturalheritage.com/education/outreach/lesson-plans/diversity.aspx

High School Human Genome Program

This Univ. of Washington program “provides professional development in the field of DNA sequencing and genomics for high school teachers” at summer workshops. Schools not in the program can still use their “virtual DNA sequencing” student activities to “gain a better understanding of how DNA sequencing works.”
http://hshgp.genome.washington.edu