Scientists 'Resurrect' the Ancient Gene That Gave Rise to the Deadliest Disease in History

The ancient gene that gave rise to the deadliest disease in history has been "resurrected" by scientists, allowing them to work out the series of events that led to the malaria parasite Plasmodium falciparum infecting humans.

Malaria kills about 435,000 people every year, with most of these being children under the age of 5. Most of these cases are caused by P. falciparum—one of the species of parasite that can cause malaria. These all originated in great apes in Africa.

"[P. falciparum] is one of the great scourges of man," Gavin Wright, from the U.K.'s Wellcome Sanger Institute, told Newsweek. "It has been said that malaria has killed more people in the history of mankind than any other disease."

Wright is lead author of a study published in PLOS Biology that shows how P. falciparum managed to switch hosts from gorillas to humans about 50,000 years ago. At this point, the parasite gained the ability to infect our red blood cells,

"Until a few years ago, the origin of P. falciparum was a mystery but it was found that it was most closely related to a Plasmodium parasite which exclusively infected gorillas," Wright said.

The genetic sequence did not explain how the parasite managed to jump from gorillas to humans. It did, however, reveal a region of the genome that appeared to have transferred, and this region encoded a gene called rh5, which we know allows the parasite to infect human red blood cells.

"The next challenge was to understand how these molecular changes could have led to the parasite being able to infect humans," Wright said.

The team reconstructed the ancestral sequence to "resurrect" the rh5 DNA sequence to show how it was transferred to humans. They created synthetic copies of this ancient gene in the laboratory in order to observe the molecular interactions that took place.

"We have taken existing gene sequences and computer-based predictions—ancestral sequence reconstruction—to turn the clock back using a type of 'molecular archaeology' to determine the likely sequence of the genes involved at the time the species switch happened," Wright explained.

Findings showed it had the ability to bind to both gorillas and humans. "This provides a molecular explanation for how the species jump could have occurred," Wright said. "We have therefore delineated a molecular pathway which explains how the ancestor of P. falciparum was able to jump host from gorillas to humans."

From this, they were able to identify a mutation that meant P. falciparum lost the ability to infect gorillas, confining it to humans.

Wright said that understanding these molecular events is important as most infectious diseases are "zoonoses." This is where a pathogen that infects other animals accumulates mutations allowing it to breach species barriers and infect humans. "By understanding the possible molecular pathways involved, although the chances are very slim, we can perform sequence surveillance of circulating parasite in the wild to try and prevent this happening again."

In terms of malaria, scientists have been looking at rh5 as a possible target for a potential vaccine. If the interaction between the parasite and this gene can be disrupted, it may stop it being able to infect the red blood cells.

"Rh5 is currently an exciting blood stage malaria vaccine target that is actively being worked on by the malaria community," Wright said. "Any additional information that could help in the development of this vaccine would be important."

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File photo of a mosquito. Researchers have discovered how the malaria parasite jumped from gorillas to humans 50,000 years ago. iStock
Scientists 'Resurrect' the Ancient Gene That Gave Rise to the Deadliest Disease in History | Health