Dramatic evolution within human genome may have been caused by malaria parasite

A genetic mutation that protects people from a common form of malaria spread like wildfire in sub-Saharan Africa about 42,000 years ago, according to a new study. Today, it’s nearly impossible to find somebody from this region who doesn’t have it. That makes the mutation one of the swiftest, strongest changes to the human genome yet seen—though it remains a mystery why this particular disease sparked such a dramatic evolutionary response.

The world’s most widespread type of human malaria is caused by Plasmodium vivax, a single-celled parasite transmitted by mosquitoes. Although less deadly than other strains, P. vivax malaria remains a disruptive disease: It infected some 16 million people across the globe in 2013. Yet across much of sub-Saharan Africa, P. vivax accounts for fewer than 5% of all reported malaria cases. That’s because about 99% of Africans living here have a variant of a gene called DARC, which shuts off a particular protein receptor on the surface of red blood cells that the parasite needs to gain entry.

To learn more about how and when this mutation spread, Omar Cornejo, a population geneticist at Washington State University in Pullman, and colleagues analyzed full genome sequences from 1000 modern individuals from 21 population centers in Africa, Asia, and Europe. The researchers then employed a computer-based simulation that predicts how certain genetic variants spread throughout a population over time given the region’s known demographics and various selective pressures.

Based on rates of genetic change, the simulation suggests the most recent common ancestor of living Africans who possessed the DARC mutation lived about 42,000 years ago, the team reports this month in PLOS Genetics . Back then, the mutation was likely just a random genetic variant possessed by a handful of people, not a functional evolutionary defense. Then something changed—quite possibly the arrival of P. vivax—and some 8000 years later, more than 99% of people in the region had the mutation, according to the simulation.

Cornejo estimates that on average during that 8000-year period, for every 100 people born without the mutation, an additional 105 would have been born with it. Assuming that widespread exposure to P. vivax meant that people who had the mutation were more likely to survive than those without it—that would make this the strongest evolutionary response yet seen in the human genome, the researchers say.

That’s a bit mysterious because the disease caused by P. vixax is much less deadly than that caused by other Plasmodium strains, says David Serre, a microbiologist at the University of Maryland’s Institute for Genome Science in Baltimore who wasn’t involved with this work. “You get sick, you stay in bed for a few weeks, and most of the time you get better.” One wouldn’t expect such a powerful evolutionary response to a relatively benign disease, he notes.

One possibility is that the disease was much deadlier thousands of years ago, and that further adaptations in our immune system have rendered it less threatening, Serre says. Another is that evolution was acting against an entirely different, as-yet-unknown disease that used the same technique as P. vivax to enter red blood cells. “The data are really good, the analysis is really good, but the story just doesn’t quite make sense yet,” he says.

Cornejo admits it’s a perplexing finding, and he agrees a heretofore unknown disease theoretically could be responsible.

Either way, he says the study should serve as a warning. Just as humans in Africa evolved to combat the parasite, the disease continues to evolve as well. Recent cases of P. vivax malaria have been reported in Madagascar, Ethiopia, and Sudan in people who possess the protective DARC mutation. It’s not yet clear whether some other factor made them susceptible to the disease, or whether the parasite evolved to find another way into red blood cells. If it’s the latter, says Cornejo, millions of people who once didn’t need to worry about P. vivax malaria might soon be at risk.