Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genomes of chimpanzee parasite species reveal evolution of human malaria

22.03.2016

Understanding the origins of emerging diseases - as well as more established disease agents -- is critical to gauge future human infection risks and find new treatment and prevention approaches. This holds true for malaria, which kills more than 500,000 people a year. Symptoms, including severe anemia, pregnancy-associated malaria, and cerebral malaria, have been linked to the parasite's ability to cause infected red blood cells to bind to the inner lining of blood vessels.

An international team led by Beatrice Hahn, MD, a professor of Medicine and Microbiology from the Perelman School of Medicine at the University of Pennsylvania, and MD/PhD student Sesh Sundararaman, used a selective amplification technique to sequence the genomes of two divergent Plasmodium species, Plasmodium reichenowi and Plasmodium gaboni, from miniscule volumes of chimpanzee blood to find clues about the evolution and pathogenicity of Plasmodium falciparum, the deadliest malaria parasite that affects people. Their findings appear this week in Nature Communications.


Female orphan chimpanzee are cared for at the Sanaga-Yong Chimpanzee Rescue Center.

Credit: Sesh Sundararaman, Perelman School of Medicine, University of Pennsylvania

African apes harbor at least six Plasmodium species that have been classified into a separate subgenus, called Laverania. Three of these Laverania species, including Plasmodium reichenowi and Plasmodium gaboni, reside in chimps, while three others, including Plasmodium praefalciparum that gave rise to Plasmodium falciparum, reside in gorillas. The gorilla origin of Plasmodium falciparum was discovered several years ago by this same international group of investigators.

"We want to know why Plasmodium falciparum is so deadly," Hahn said. "The answer must lie in the blueprint -- the genome -- of its chimpanzee and gorilla cousins. We also want to know how and when the gorilla precursor of Plasmodium falciparum jumped into humans, and why this happened only once."

Parasites infecting humans and great apes share genes that allow them to hide from the host's immune system, adhere to tissues, and cause disease. Better understanding the evolution of human malaria virulence provides potential new targets for drugs and vaccines.

Coauthor Dustin Brisson, PhD, a professor of Biology at Penn, initially developed the selective amplification method to sequence bacterial genomes. Sundararaman calls applying this new approach to malaria research "one of the paper's most important contributions." Using this technique, the team was able to generate high quality Laverania genome sequences by using small amounts of unprocessed blood collected from chimpanzees living in sanctuaries during routine health screens.

The chimpanzee parasite genomes contain a goldmine of information about the evolutionary origins of the malaria parasites infecting humans. One of the first things to emerge from genome-wide analyses was that the parasites indeed represent distinct, non-interbreeding species.

In addition, members of each chimpanzee parasite species display about 10 times more genetic diversity than do human parasites. "The chimpanzee parasites really highlight the lack of diversity in Plasmodium falciparum," said co-author Paul Sharp, PhD, an evolutionary biologist from the University of Edinburgh and long-term collaborator of the Hahn team. "This is most likely because these parasites went through a severe bottleneck when first transmitted to humans, perhaps within the past 10,000 years."

By comparing the different parasite genomes the team also found an expansion of a multi-gene family, which governs red blood cell remodeling and therefore helps the parasite to evade host immune cells as well as clearance by the spleen. "The remodeling process is a key part of severe malaria pathology in human Plasmodium falciparum infections," explained coauthor Julian Rayner, PhD, a malaria researcher at the Wellcome Trust Sanger Institute and long-term member of the research team. "The expansion of this gene family from a single gene in all other Plasmodium parasites to up to 21 genes in Laverania suggests that remodeling evolved early in the radiation of this group of primate parasites and contributed not only to their unique biology but perhaps also to their successful expansion."

"'We also found a short region of the genome, including two essential invasion genes, where Plasmodium falciparum was much more different from its close relatives than we expected," said Lindsey Plenderleith, PhD, a postdoctoral fellow at the University of Edinburgh, who together with Sundararaman compared and annotated the various parasite genomes. Further analysis yielded the surprising finding that this fragment of DNA was horizontally transferred -- from one species to another -- into the gorilla ancestor of Plasmodium falciparum.

"It is tempting to speculate that this unusual event somehow predisposed the precursor of Plasmodium falciparum to colonize humans," added Hahn. "However, this gene transfer clearly is not the entire story."

Although the origin of Plasmodium falciparum is now well-established from past research by this group, nothing is known about the circumstances that led to its emergence. "Coaxing entire parasite genome sequences out of small quantities of unprocessed ape blood will help us to better understand what happened and whether it can happen again," Sundararaman said.

"It's an exciting time to study Plasmodium species that cannot be cultured and have thus been neglected because of the difficulty of obtaining sufficient quantities of DNA for whole genome sequencing," Hahn said. The team plans, as a next step, to use the now validated select genome amplification technique to sequence additional ape parasite genomes to identify host-specific interactions and transmission requirements, thereby uncovering vulnerabilities that can be exploited to combat human malaria.

Colleagues from the Sanaga-Yong Chimpanzee Rescue Center, IDA-Africa, Portland, OR, and the Institut de Recherche pour le Developpement (IRD), Montpellier, France, were also coauthors.

###

This work was supported, in part, by grants from the National Institutes of Health (R01 AI097137, R01 AI091595, R37 AI050529, T32 AI007532, P30 AI045008), the Burroughs Wellcome Fund (1012376), the Agence Nationale de Recherche sur le Sida (ANRS 12125/12182/12255), the Agence Nationale de Recherche (ANR 11 BSV3 021 01, Project PRIMAL) and the Wellcome Trust (098051).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

Karen Kreeger | EurekAlert!

Further reports about: Plasmodium Plasmodium falciparum falciparum genes human malaria malaria parasite parasites

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>