Indirect Approach Uses Yeast to Identify Function of Malaria Genes

By using DNA segments isolated from a less deadly form of the malaria-causing parasite Plasmodium, researchers have developed an indirect method for assigning functions to the genes of the lethal human parasite P. falciparum.

Although the complete genome of P. falciparum was sequenced in 2002, its high content of adenine and thymine (A and T) moieties has made it almost impossible to determine the precise function of any of its genes.

To overcome this obstacle investigators at National Jewish Health (Denver, CO, USA) and Yale University (New Haven, CT, USA) constructed a cDNA library from P. knowlesi, which has a lower A + T content compared with P. falciparum. Use of DNA segments from P. knowlesi allowed the investigators to take advantage of the large repertoire of genetic tools available for Saccharomyces cerevisiae, which makes this yeast an ideal system for large-scale functional complementation analyses of parasite genes. After establishing the functions of the P. knowlesi genes they could then match them to corresponding genes in P. falciparum.

The investigators reported in the January 2, 2012, issue of the Journal of Biological Chemistry that they had identified the malaria genes involved in the decarboxylation of phosphatidylserine. The gene, phosphatidylserine decarboxylase, directs the formation of a protein unique to malarial parasites and is a potential therapeutic target.

“The malarial genome has been a black box. Our technique allows us to open that box, so that we can learn what genes in the most lethal human parasite actually do,” said senior author Dr. Dennis Voelker, professor of medicine at National Jewish Health. “This could prove tremendously valuable in the fight against a disease that has become increasingly drug-resistant. This technique could lead to an explosion in knowledge about malaria and the parasite that causes it.”

Related Links:
National Jewish Health
Yale University