Researchers have reconstructed how the deadliest form of the malaria pathogen jumped from animal to human. Thus, about 50,000 years ago, Plasmodium falciparum acquired the ability to infect red blood cells in humans.
The ancestor of today's pathogen was actually specialized in gorillas, writes the team around Gavin Wright of the British Wellcome Sanger Institute in Cambridge in the magazine "Plos Biology". His ability to infest even humans, the dangerous pathogen apparently received a gene sequence from a gorilla parasite, which built into his DNA.
The foreign genetic sequence contains a gene that produces the protein RH5. This can bind to receptors in human red blood cells and infect them.
P. falciparum is made up of seven representatives of the sub-group Laverania, which originated in Africa and specialize mainly in apes: three of them infect only chimpanzees, three more only gorillas. Only P. falciparum specializes in humans.
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To unravel this mystery, the researchers around Wright compared the genome of the seven Laverania species. They came across a sequence that seems to have passed from the gorillas-specific pathogen P. adleri to the ancestors of P. falciparum.
The researchers suspect that the gene was transferred when a gorilla was simultaneously infected with the two Plasmodium species P. adleri and the ancestor of P. falciparum. In this case, genes were probably exchanged between the pathogens. Such events are generally very rare, the team emphasizes.
Deadliest disease in human history
"In human history, P. falciparum has been responsible for more deaths than any other disease," says Wright. Currently more than 400,000 people die each year from infectious diseases, most of them children under the age of five.
Several Plasmodium species cause human malaria. By far the most dangerous is the malaria tropica, which is native to Africa in particular, and is caused by P. falciparum. According to the researchers, it caused 99.7 percent of all malaria cases in Africa in 2017.
To better understand the role of the gene introduced in the ancestors of P. falciparum, the researchers created synthetic copies of the genomic strand. According to the analysis, the protein RH5 can bind to receptors in red blood cells of gorillas as well as humans. "This immediately provided a molecular explanation for how P. falciparum developed the property of infecting humans," says first author Francis Galaway.
Later, the pathogen lost the ability to infect gorillas through a mutation in an amino acid of the protein and was thus specialized only in humans.
Skipping diseases from the animal kingdom to humans is by no means unusual. Other examples of such zoonoses are influenza, HIV, Ebola, Sars or rabies.
