Navigation Links
Penn researchers show new evidence of genetic 'arms race' against malaria
Date:6/9/2011

PHILADELPHIA For tens of thousands of years, the genomes of malaria parasites and humans have been at war with one another. Now, University of Pennsylvania geneticists, in collaboration with an international team of scientists, have developed a new picture of one way that the human genome has fought back.

The international team was led by Sarah Tishkoff, a Penn Integrates Knowledge professor with appointments in the genetics department in Penn's Perelman School of Medicine and the biology department of biology in the School of Arts and Sciences, and Wen-Ya Ko, a postdoctoral fellow in the genetics department at the medical school. They performed a genetic analysis of 15 ethnic groups across Africa, looking for gene variants that could explain differing local susceptibility to malaria.

Their research will be published online in the journal American Journal of Human Genetics on June 2.

Malaria remains one of the deadliest diseases on the planet, annually killing about a million people, 90% of whom live in Africa. Different populations show different responses to the parasites that cause malaria; the team conducted the largest cross-population comparison ever on a pair of genes related to malaria's ability to enter red blood cells.

"When you try to identify the variants that are associated with disease susceptibility, it's important to do a very fine scale study," Ko said. "Different populations evolve independently, to a certain degree, so different populations can come up with unique mutations."

The life cycle of malaria depends on infecting red blood cells by binding to their surfaces, which is why mutations, such as sickle cell anemia, that change the overall shape of those cells are thought to have experienced positive selection.

"Both host and the parasite try to fight back with mutations; it's a co-evolution arms-race that leaves a signature of selection on the genes," Ko said. "We've identified several single-nucleotide polymorphisms that are candidates for that signature."

Across the 15 population sets, the researchers focused on polymorphisms in a pair of genes that code for proteins called glycophorin A and glycophorin B. These proteins exist on the surface of red blood cells, and changes to their shape affect the ability of the parasite causing malaria to bind to them and to infect the cells.

There are, however, two conflicting theories of why changes to glycophorin shape influence rates of malaria. One theory suggests that glycophorin A acts as a decoy, making itself more attractive to binding so that pathogens don't infect more vulnerable cells. Another theory suggests that glycophorin A mutates so that malaria parasites can't bind at all.

The researchers observed differing patterns of natural selection acting on the different regions of the two genes. They noted an excess of genetic variation being maintained in the region of glycophorin A that plays a critical role of entry of the malaria parasite into the blood cell.

"This signature of selection was strongest in populations that have the highest exposure to malaria," Tishkoff said.

In addition, the researchers identified a novel protein variant at glycophorin B in several populations with high levels of malaria that may also be a target of natural selection.

Comparisons to chimpanzee and orangutan genomes showed that these mutations occurred after the human lineage split from these closely related primates. But a process known as "gene conversion," in which similar genes can acquire mutations from one another during cell division, complicates tracking the exact history of the mutation's spread.

"The genes for glycophorin A and B arose through gene duplication. They are more than 95 percent similar to each other on the sequence level," Ko said. "Because they are so similar, sequences of A might bind to B during recombination, which means a mutation that occurs on one can be shared with the other."

That aspect of gene conversion may be a key to helping humans in the genetic arms race against malaria.

"The parasite's genome is very highly mutable, and its generation time is short, as compared to humans, so having more mutations more quickly is helpful in keeping up," Ko said. "This is one tool in the arms race. It may not win the war, but it's another way to increase variation."

A better understanding of the interplay between the genes of the malaria parasite and that of its human hosts could also give researchers an artificial advantage drugs or vaccines in the fight against the disease.

"Any new information about how malaria infects cells and how humans have evolved natural defense mechanisms against that infection adds to the body of knowledge about the pathology of malaria," Tishkoff said. "This information could aid in the development of more effective treatments against malaria."


'/>"/>

Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

Related biology news :

1. Penn researchers develop biological circuit components, new microscope technique for measuring them
2. Researchers discover potential cause of chronic painful skin
3. University of Iowa researchers identify caffeine-consuming bacterium
4. USC researchers discover genetic mutation causing excessive hair growth
5. Eating dirt can be good for the belly, researchers find
6. Caltech researchers build largest biochemical circuit out of small synthetic DNA molecules
7. UNH researchers receive grant for pioneering carbon cycle model
8. Penn researchers help nanoscale engineers choose self-assembling proteins
9. Researchers from the Viikki Biocenter discover how plants control the formation of wood cells
10. Researchers solve mammoth evolutionary puzzle: The woollies werent picky, happy to interbreed
11. What is a laboratory mouse? Jackson, UNC researchers reveal the details
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... , March 23, 2017 The report "Gesture Recognition and ... Industry, and Geography - Global Forecast to 2022", published by MarketsandMarkets, the market ... CAGR of 29.63% between 2017 and 2022. Continue ... ... ...
(Date:3/22/2017)... NEW YORK , March 21, 2017 /PRNewswire/ ... Customer Marketing Cloud used by retailers such as ... in its platform — Product Recommendations and Replenishment. Using ... to give more personalized product and replenishment recommendations ... purchases, but also on predictions of customer intent ...
(Date:3/20/2017)... PMD Healthcare announces the release of its ... System (WMS), a remote, real-time lung health monitoring and ... is a Medical Device, Digital Health, and Chronic Care ... innovative solutions that empower people to improve their healthcare ... developed the first ever personal spirometer, Spiro PD, which ...
Breaking Biology News(10 mins):
(Date:4/20/2017)... ... April 20, 2017 , ... Husson University will be ... growing body of knowledge during its Eighth Annual Research and Scholarship Day ... Darling Atrium. During the event, undergraduates, graduate students, and faculty members from all ...
(Date:4/20/2017)... ... April 20, 2017 , ... Open Therapeutics and ... (IP) sharing and commercialization model. , The Center for Advancing Innovation helps institutions ... this effort is bringing the IP to the attention of the entrepreneurial community ...
(Date:4/19/2017)... ... April 18, 2017 , ... A number of new instruments have recently emerged ... of the Protein and Cell Analysis Education Webinar Series , will focus on ... in current and future applications. , Many flow cytometers have unique capabilities and ...
(Date:4/19/2017)... New York, NY (PRWEB) , ... April 19, ... ... working to combat Clostridium difficile (C. diff) infections through education and advocacy. ... lost her life to a C. diff infection, the foundation has become the ...
Breaking Biology Technology: