An international research team announced today the completion of a genome-wide map that charts the genetic variability of the human malaria parasite Plasmodium falciparum. Published in the December 10 advance online edition of Nature Genetics, the study reveals striking variation within the pathogen's genome, including an initial catalog of nearly 47,000 specific genetic differences among parasites sampled worldwide. These differences lay the foundation for dissecting the functions of important parasite genes and for tracing the global spread of malaria. Led by scientists at the Harvard School of Public Health and the Broad Institute of MIT and Harvard, together with researchers in Senegal, the work has already unearthed novel genes that may underlie resistance to current drugs against the disease.
"Malaria remains a significant threat to global public health, driven in part by the genetic changes in the parasite that causes the disease," said senior author Dyann Wirth, a professor and chairman of the department of immunology and infectious diseases at the Harvard School of Public Health and the co-director of the Broad Institute's Infectious Disease Initiative. "This study gives us one of the first looks at genetic variation across the entire malaria parasite genome — a critical step toward a comprehensive genetic tool for the malaria research community."
Plasmodium falciparum — the deadliest of the four parasites that cause malaria in humans — kills one person every 30 seconds, mostly children living in Africa. Despite decades of research, the genetic changes that enable it to escape the body's natural defenses and to overcome malaria drugs remain largely unknown.
To gain a broad picture of genetic variability — worldwide and genome-wide — the scientists analyzed more than 50 different P. falciparum samples from diverse geographic locations. This includes the complete genome sequencing of two well-studied samples as well as extensive DNA analyses of 16 additional isolates. The work is one of three large-scale studies of the parasite's DNA that appear together in Nature Genetics, and it represents a collaborative effort among Boston area researchers and a scientific team led by Souleymane Mboup, a professor at the Cheikh Anta Diop University in Senegal where malaria is endemic. "We are grateful for the contributions of our colleagues in Senegal. They are a crucial part of this collaboration," said Wirth.
By comparing the DNA sequences to each other and to the P. falciparum genome sequenced in 2002, the researchers uncovered extensive differences, including ~ 47,000 single letter changes called single nucleotide polymorphisms (SNPs). This represents more than double the expected level of diversity in the parasite's DNA. Although there are probably many more SNPs to be found, this initial survey — like the recent HapMap project in humans — provides a launching point for future systematic efforts to identify parasite genes that are essential to malaria.
"The roles of most of the malaria parasite's genes are still not known," said first author Sarah Volkman, a research scientist at the Harvard School of Public Health. "An important application of this new tool will be in pinpointing the genes that are vital to the development and spread of malaria."
One of the tool's strengths is its ability to reveal evolutionary differences among parasites. This information can shed light on the genes responsible for malaria drug resistance — a major obstacle to adequate control of the disease. Using the genetic map to compare parasites exposed to different anti-malarial drugs, the scientists identified a novel region that is strongly implicated in resistance to the drug pyrimethamine, and also confirmed a region of the genome known to be involved in chloroquine drug resistance.
"The same genetic principles used to study human evolution can provide important clues about malaria," said first author Pardis Sabeti, a postdoctoral fellow at the Broad Institute. "This tool has already yielded insights into the genetic changes that correlate with different drug treatments, pointing us to genes that may contribute to drug resistance."
The map can also define the genetic landscapes of different parasite populations. Applying it to parasites from various continents, the scientists discovered greater DNA variability among P. falciparum samples from Africa relative to those from Asia and the Americas. This knowledge guides the selection of genetic markers to track the transmission of distinct parasites, particularly ones that are virulent or drug resistant. It also lays the groundwork for connecting parasite genes with traits that vary geographically and bolster malaria's foothold in many parts of the world.
"Genomic tools have largely been applied to first-world diseases up to now. This project underscores the power and importance of applying them to the devastating diseases of the developing world," said Eric Lander, one of the study's authors and the director of the Broad Institute. "By joining forces among scientists in the U.S., Africa and elsewhere, it should be possible to rapidly reveal the genetic variation in malaria around the world. Knowing the enemy will be a crucial step in fighting it."
Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin
Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology