a red blood cell; Credit: St Jude
Children’s Research Hospital
Scientists have generated a 3D model of the human malaria parasite genome at 3 different stages in the parasite’s life cycle, according to a report in Genome Research.
The team said this model of Plasmodium falciparum is the first to be generated during the progression of a parasite’s life cycle.
“We successfully mapped all physical interactions between genetic elements in the parasite nucleus,” said study author Karine Le Roch, PhD, of the University of California, Riverside.
“To do so, we used a chromosome conformation capture method, followed by high-throughput sequencing technology—a recently developed methodology to analyze the organization of chromosomes in the natural state of the cell. We then used the maps of all physical interactions to generate a 3D model of the genome for each stage of the parasite life cycle analyzed.”
The model revealed that genes that need to be highly expressed in the malaria parasite—for example, genes involved in translation—tend to cluster in the same area of the cell nucleus, while genes that need to be tightly repressed—for example, genes involved in virulence—are found elsewhere in the 3D structure in a “repression center.”
The 3D structure had one major repression center. And the researchers found that virulence genes, which are all organized into that one repression center in a distinct area in the nucleus, seem to drive the full genome organization of the parasite.
“If we understand how the malaria parasite genome is organized in the nucleus and which components control this organization, we may be able to disrupt this architecture and disrupt, too, the parasite development,” Dr Le Roch said.
“We know that the genome architecture is critical in regulating gene expression and, more important, in regulating genes that are critical for parasite virulence. Now, we can more carefully search for components or drugs that can disrupt this organization, helping in the identification of new antimalaria strategies.”
Dr Le Roch’s lab is now looking at other stages of the malaria life cycle in order to identify components responsible for the 3D genome architecture.
“The importance of the genome architecture was initially thought to be critical for only higher eukaryotes,” she explained. “But we found, to our surprise, that the genome architecture is closely linked to virulence, even in the case of the malaria parasite.”
