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Study Suggests Malaria Parasites Accompanied Humans Out-of-Africa

By Andrea Anderson

NEW YORK (GenomeWeb News) – A genetic study appearing in the early, online edition of Current Biology yesterday suggests malaria parasites were infecting modern humans prior to their migration out of Africa some 60,000 to 80,000 years ago.

By sequencing two housekeeping genes in more than 500 P. falciparum parasites from around the world and SNP patterns in these genes, an international research team has garnered evidence suggesting the genetic diversity of malaria parasites is highest in Africa and decreases with distance from Africa — a pattern that roughly corresponds to diversity patterns in human populations.

"The expansion of malaria probably was not anything linked to specific mutations," senior author Francois Balloux, an infectious disease epidemiology researcher at Imperial College London's MRC Centre for Outbreak Analysis and Modeling, told GenomeWeb Daily News. "When the host expanded they just were stowaways or hitchhiked."

Past studies have uncovered some clues about how genetics influence malaria infections and drug response. For instance, a genome-wide association study published earlier this year offered clues about how genetic patterns relate to drug resistance in malaria populations around the world.

Even so, there's still debate about the parasite's genetics, history, and age, Balloux and his co-authors explained, with previous research putting its divergence at anywhere from 10,000 to 300,000 years ago.

In an effort to clarify P. falciparum genetic patterns and gain a clearer understanding of their relationship with humans, Balloux and his collaborators sequenced two genes — the serca ATPase gene and the adsl adenylosuccinate lyase gene — from blood samples of infected individuals in nine countries in sub-Saharan Africa, southeast Asia, Oceania, and South America.

The serca and adsl genes were selected because they are thought to be fairly diverse, but don't seem to be under selection due to antimalarial drugs, Balloux explained.

When the team sifted through data on 519 P. falciparum isolates, looking at the patterns for 49 SNPs in the serca gene and 14 SNPs in adsl, they found that P. falciparum genetic patterns resembled those in human populations: parasites from Africa showed the greatest genetic diversity and genetic diversity generally decreased with greater distance from Africa.

That argues against specific adaptations to human hosts in Old World populations, Balloux explained, and instead suggests that when human populations expanded out of Africa roughly 60,000 to 80,000 years ago they took malaria parasites with them.

"My interpretation is really that this is a completely passive dispersal following humans," he said. "Essentially the host just expanded its range and the malaria just followed."

Even so, malaria parasites did not manage to move to all of the areas colonized by humans during these early migrations. For example, researchers noted, the parasites would not have been able to move across the Bering Strait into the Americas with humans 15,000 to 20,000 years ago due to temperature limitations.

"[A] joint colonization P. falciparum together with humans into the Americas is highly implausible," Balloux and his co-authors wrote. "Thus, the Americas have probably been colonized by this parasite far more recently, possibly through the slave trade."

Such additional migrations from Africa to the Americas, in turn, may help account for the fact that genetic diversity in parasites in Brazil was higher than anticipated, resembling that detected in Tanzania.

Nevertheless, the overall findings appear to be consistent with P. falciparum movement from Africa at around the same time as modern humans.

Moreover, Balloux noted, the genetic results suggest P. falciparum originated somewhere in central sub-Saharan African — likely in and around the Great Lakes region.

In addition to the information that such studies are providing about malaria history, those involved in the study argue that exploring P. falciparum's genetic diversity may also offer clues to understanding how malaria parasites outwit human immune defenses.

For their part, the researchers are continuing to analyze data on additional genes investigated in the current study, Balloux said. They are also exploring P. falciparum genetics in even more locales around the world and are currently collecting samples in other parts of Africa, Vietnam, and Iran.

Down the road, the researchers also hope to incorporate whole genome sequencing into their international malaria parasite sampling efforts — a goal that Balloux believes is technically feasible once sequencing becomes more economical.

Genome-wide sequencing "allows [us] to detect additional drug resistance mutations that are unknown and help to find possible targets for vaccines," he said.

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