A new paper听听today in the journal听Nature Communications听and co-authored by a researcher at the University of Colorado Boulder鈥檚 BioFrontiers Institute, looks at the genetic strategy used by the human malaria parasite and how old it is from an evolutionary perspective.
Aaron Clauset of the BioFrontiers Institute and an assistant professor of computer science at CU-Boulder, was part of a team that analyzed genetic data from apes and found that the genetic strategy used by the parasites that cause a malaria infection is the same, whether the disease is in humans or other primates. The team compared the genes of ape malaria parasites with those of human malaria to determine if the two use the same strategies for prolonging the disease.
Malaria is a complex disease process where the parasite invades red blood cells and the disease produces proteins on the cell鈥檚 surface. Genes called 鈥渧ar genes鈥� create these proteins, which are recognized by the immune system鈥檚 antibodies. These antibodies bind onto the cell surface then kill the cell that contains the parasite. To confuse the host鈥檚 immune system, the parasite switches the types of var genes it uses on the surface of the cell so that antibodies can鈥檛 bind with the cell surface and kill the host cell and parasite. In addition, the parasite鈥檚 var genes, once they are in the cell, mix genetic information in a process called recombination so that antibodies are faced with an almost infinite number of different proteins the prevent the host cell from being killed.
The study, led by Daniel Larremore, an Omidyar Fellow at the Santa Fe Institute and a researcher at the Center for Communicable Disease Dynamics (CCDD) and the Department of Epidemiology at Harvard School of Public Health, used fecal and blood samples from wild chimpanzees and western lowland gorillas, as well as chimpanzees living in a sanctuary to better understand the patterns in the var genes. They looked at similarities between the genes that are implicated with severe malaria in humans and those in other primate malaria parasites. The fecal and blood samples were leftover samples collected for previous genetic studies.
The team analyzed a small region of the gene sequence using network techniques and identified patterns that were consistent across different types of primate malaria parasites. The research team analyzed 369 new sequence fragments from ape parasite species of wild living and sanctuary apes and added 353 previously known sequences. Larremore received his PhD in applied math from CU-Boulder. After receiving his PhD, he had a joint postdoctoral position in Clauset鈥檚 lab and Harvard鈥檚 CCDD.
鈥淢alaria is an important system to work on,鈥� says Clauset. 鈥淚t鈥檚 both a major public health issue, especially in developing countries and places where climate change is bringing it back, and a fascinating evolutionary system. The malaria parasite has an ever-changing bag of genetic tricks it uses to prolong an infection, and understanding how it does this will help develop better treatments for this disease and help us understand how some other diseases, like HIV, maintain their evolvability over long periods of time. 鈥�
Malaria is difficult to treat in humans because the malaria parasite has an extensive and ever-changing set of tricks to avoid detection by the immune system. Apes, humans, and even birds and reptiles, have their own version of malaria. This study showed that malaria in all primates (including humans) use the same genetic system to evolve new ways to avoid detection by the host's immune system. The wild primate blood samples showed several strains of malaria. Because the disease evolved with primates, their immune systems are equipped to manage it so it causes fewer, less severe symptoms. Humans suffer much more severe symptoms than primates, and even death, from the disease. The researchers believe this is because malaria jumped from primates to humans after the two split from a common ancestor: Human immune systems have had less time to evolve to manage the disease.
鈥淥ur results show that human malaria uses the same genetic strategy as ape malaria to prolong an infection. This insight may help us identify components of this immune evasion system that could become targets for a vaccine,鈥� says Clauset. 鈥淚t may also help us understand other diseases that use similar strategies, like the pneumococcus and HIV.鈥�
The study was supported by grants from the National Institutes of Health and the Wellcome Trust.
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Mosquitos are the primary disease vectors for the malaria parasite. 听Photo by U.S.D.A / Wikipedia.
