BioWorld International Correspondent

LONDON - The newly available genome sequence of the intestinal parasite Giardia lamblia could lead to alternative therapies for treating the diarrhea it causes, as well as better understanding of many of the metabolic reactions that take place in human cells.

Staffan Svärd, an associate professor at Uppsala University in Sweden, told BioWorld International: "The major finding is that the organism has a very simple genetic structure, and because it is a eukaryote and therefore related to ourselves, its genes and proteins can give us clues to what are the most important genes and proteins in our own metabolic processes."

Svärd is a co-author of the paper reporting the genome sequence, which was published in the September 28, 2007, issue of Science. The title of the paper is "Genomic Minimalism in the Early Diverging Intestinal Parasite Giardia lamblia."

Analysis of the genome, which was sequenced by an international team of researchers led by scientists at the Marine Biological Laboratory in Woods Hole, Mass., and funded by the National Institute of Allergy and Infectious Diseases, shows that the parasite differs in several ways from other organisms when copying and reading DNA. It also lacks several common signal proteins, but has many enzymes whose function is currently unknown.

The life cycle of Giardia takes place both in water and in the gut of humans and animals. In water, it exists as a hardy, highly infectious cyst that can survive for months. When the cyst is swallowed by a human or an animal, the trophozoite form of the parasite hatches out. That is a swimming and feeding form. It does not invade tissues or cells, but attaches itself to cells, takes in nutrients and multiplies.

Some trophozoites detach themselves from the intestinal wall, pass into the large bowel, transform back into cysts and are passed out in the stools. When they contaminate water or food, the life cycle is completed.

Giardia infection can cause diarrhea, which may last two to six weeks, although it does not do so in everyone. Even in those without symptoms of nausea, diarrhea, bloating and abdominal cramping, it may cause difficulty in absorbing nutrients, poor growth and development, and weight loss.

There are an estimated 20,000 reported infections in the U.S. each year, many of them in people who drank from untreated water supplies, and in small children in day-care facilities. In European countries, most cases are in people who have been traveling abroad.

The infection is economically important in agriculture, as it also causes weight loss and poor development in sheep and cattle.

One reason for sequencing the genome of Giardia, Svärd said, was to settle the debate about why the parasite has so few enzymes and proteins. There are two theories to explain that: Either Giardia diverged from other eukaryotes a very long time ago and has remained very simple, or perhaps it lost much of its original complexity during its adaptation to its parasitic lifestyle.

Mitchell Sogin, director of the Marine Biological Laboratory's Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, and the first author on the paper, said: "Earlier molecular analyses suggested that Giardia represents a very early diverging lineage in the evolutionary history of eukaryotes. Giardia's genome content and architecture support these theories about the parasite's ancestral character."

The analysis showed, for example, that where human cells have about 50 components to carry out a particular metabolic process, Giardia only has about five. Svärd said, "This is very helpful because it tells us which proteins are the most important ones for each basic process."

Even though it is possible to see homologous proteins in Giardia and in humans, the proteins are very different, he added. "This tells us what are the most important parts of each protein," Svärd explained. "This is very useful for everyone working in all different systems in biology."

Such studies are crucial for this particular organism, he added, because conventional approaches involving knocking out single genes are not possible in Giardia - the parasite has two diploid nuclei in each cell and therefore four copies of every gene.

Study of Giardia's proteins will, Svärd predicted, make it possible to identify those which could provide targets for new drug therapies, or which might help in the development of vaccines.

"We can also see all the genes that are involved in antigenic variation - we can see what the common antigenic variants are and which are the rarer ones. If we can block the process of antigenic variation, of course, then we can block the infection, because blocking antigenic variation would allow the immune system to eliminate the parasite," Svärd said.

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