Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genome of a monkey-human malaria parasite: surprises from Plasmodium knowlesi genome sequence

09.10.2008
Researchers have decoded the genome of a malaria parasite that has a host range from monkeys to man. Identified originally in monkeys, the parasite was first reported in a human infection just over 40 years ago.

Until recently, four species were held responsible for human malaria infections: P. falciparum, P. vivax, P. ovale, and P. malariae. P. knowlesi is increasingly recognised as the fifth and emerging human malaria parasite, which is particularly prevalent in South East Asia and can cause potentially life threatening malaria. Recent surveys suggest that many P. knowlesi infections have been misdiagnosed by microscopy as P. malariae, resulting in gross underestimates of its prevalence.

The genome sequence reveals a dramatic example of 'molecular mimicry' that is likely to be crucial for survival and propagation of the parasite in the body. Remarkably, the team found several members of a large gene family that contain sequence signatures that closely resemble a key human gene involved in regulation of the immune system. The parasite versions of the human protein are thought to interfere with recognition of infected red blood cells.

In addition to this uniquely expanded group of genes, P. knowlesi has a fundamentally different architecture of the genes involved in 'antigenic variation' compared to other malaria parasites. The study also emphasizes the fact that, although 80% of genes are shared among all sequenced malaria parasites, each species may have a unique set of tricks and disguises that help it to escape host responses and to keep itself ahead in the host–parasite interaction.

"P. knowlesi has thrown up several surprises. Our study demonstrates the power of sequencing additional malaria genomes to unravel as yet undiscovered and fascinating aspects of the biology of malaria parasites" says Dr Arnab Pain, the first author in the study and the project manager at the Wellcome Trust Sanger Institute.

"Unusually, the key genes that we think help the parasite to evade detection and destruction by host defences are scattered through the genome. In the other species we have examined, these genes are most often near the tips of the chromosomes".

The phenomenon of 'antigenic variation' - where the parasite constantly changes the coat of parasitized red cells in order to avoid recognition by the host - was also first discovered in P. knowlesi. Moreover, it can be studied and grown in the lab, making it ideal to understand it's basic biology such as how it invades red cells.

Identified initially as a monkey parasite, P. knowlesi had been identified in only two cases of human infection before 2004. However, at that time, Professor Balbir Singh and colleagues developed DNA-based detection methods and examined samples from malaria patients in Malaysia. They showed that almost all cases of what was thought to be infection with the human parasite P. malariae were due to infection with the 'monkey' parasite P. knowlesi.

"Rapid and appropriate treatment is vital in cases of malaria," says Professor Balbir Singh, Director of the Malaria Research Centre at the Faculty of Medicine and Health Sciences, University Malaysia Sarawak, "but before the development of molecular detection methods, we had been hampered by our inability to distinguish between P. knowlesi and the benign P. malariae parasites by microscopy. This parasite multiplies rapidly and can cause fatal human infections, so it is vital that doctors are aware that P. knowlesi is the fifth cause of human malaria.

"The genome sequence of what has been considered to be a 'model' for human malaria becomes much more significant with our findings of the widespread distribution and high levels of human infections with P. knowlesi."

P. knowlesi is an important model for studying the way that malaria parasites interact with host cells. It is a robust species in which invasion of red blood cells can be examined in detail. The genome sequence provides an updated catalogue of proteins that might help the parasite in these first stages of infection: the team identified novel regions in the genome that help to understand the regulation of these key genes and the transport of their proteins to the red cell surface.

Switching of surface proteins is a key defence mechanism for malaria parasites, as well as being essential for successful transfer between human and mosquito host, but the mechanisms of switching remain unclear.

"This is our first view of a monkey malaria parasite genome. It brings us intrigues and surprises - as well as new resources to help in the fight against malaria," says Dr Alan Thomas, Chairman of the Department of Parasitology, Biomedical Primate Research Centre in RIJSWIJK, Netherlands. "P. knowlesi is closely related to the second-most common cause of human malaria, P. vivax. With our new understanding of the genetic architecture of both parasites, we will more efficiently translate our studies on P. knowlesi to other human parasites.

"Just as important, the genome will help in understanding human cases of knowlesi malaria."

It is thought that P. knowlesi is a zoonotic malaria parasite that is transmitted by mosquitoes of the Anopheles leucosphyrus group that feed on humans and monkeys.

The function of the majority of Plasmodium proteins remains unknown. Comparison with the other malaria parasites will help to understand the differences in pathology and the mechanisms they share in interacting with the human, monkey or mosquito hosts.

The current work is published in Nature along with a companion study, deciphering the genome of another human malaria parasite Plasmodium vivax. That study was led by scientists at the New York University School of Medicine and the J Craig Venter Institute [formerly The Institute for Genomic Research (TIGR )] of Rockville, Maryland, USA. The Sanger Institute is also sequencing the remaining two human-infecting Plasmodium species. The genome of P. falciparum was deciphered in 2002.

Don Powell | alfa
Further information:
http://www.sanger.ac.uk

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>