Researchers have described the complete genome (genetic sequence) of Giardia, the most common human parasite that causes more than 20,000 intestinal infections a year, paving way for the development of new drugs to combat this persistent infection.
The intestinal infection is contracted through contaminated drinking or swimming water. The Giardia parasite lives in the human intestine in swimming and feeding form called a trophozoite, which is eventually expelled through the stools. Outside the body, Giardia takes the form of a highly infectious cyst that can live for weeks in water, soil, food, or on other surfaces.
"Even though there are treatments now available, a number of people get chronic giardiasis, which is difficult to eliminate. So there is interest in new treatments," said Hilary Morrison, Ph.D., of the MBL's Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, the first author on the paper.
"Although not life threatening, Giardia is a rather fastidious parasite and quite important from an economical viewpoint worldwide and in the United States, where it constitutes a major cause of diarrhoeal disease in children in day-care centers," said Mitchell Sogin, Ph.D., director of the Josephine Bay Paul Center and leader of the Giardia study.
Analysis of the Giardia genome revealed several unusual proteins that are promising drug targets, 'These proteins are different enough from human proteins that if you affect them with a drug, it's not going to affect the human counterparts," she says.
"Drugs can be devised that will interfere with the parasite's ability to replicate, or to move or bind in the small intestine, or to exist at all," Morrison said. The MBL team also investigated the evolutionary history of this ancient parasite. Giardia is a single-celled eukaryote, meaning its cell has a nucleus, as do the cells of humans and most other multicellular organisms. But the Giardia genome is compact compared to other eukaryotes, with simplified machinery for several basic processes, such as DNA replication and RNA processing.
If the Giardia genome had originally been complex and experienced gene loss over evolutionary time, Morrison says, one would expect to see parts of the machinery intact and parts missing. This, however, wasn't the case. "It looks like the genome was just simpler to begin with. The authors hypothesize that Giardia diverged from other eukaryotes more than a billion years ago," Morrison said.
"We embarked upon this genome project because of its importance to human health and suggestions from earlier molecular analyses that Giardia represents a very early-diverging lineage in the evolutionary history of eukaryotes," Sogin said.
"Giardia's genome content and architecture support these theories about the parasite's ancestral character," he added. Another important finding, Sogin said is that the genes that allow Giardia to evade the human immune response are organized differently than in other parasites. In the host intestine, Giardia eludes an immune system attack by shifting the proteins it displays on its surfaces. The genes for these surface proteins are scattered throughout the Giardia genome rather than found in clusters, as in other parasites.
The study is published in the September 28 issue of Science.