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Sequencing Analysis Traces Origins of Malaria-Causing Parasite to Southeast Asia

NEW YORK — A new sequencing analysis suggests that the malaria-causing Plasmodium vivax may have originated in Southeast Asia.

P. vivax is the most common malaria parasite and causes between 12 million and 22 million cases of malaria a year, especially in Central and Southeast Asia, though it is not as deadly as P. falciparum. But the origins of P. vivax are unclear, as there are two competing theories for where it arose.

The out-of-Africa scenario is supported by a recent study that found a P. vivax-like­ species among chimpanzees and gorillas in Africa as well as the high prevalence of Duffy negativity among sub-Saharan African human populations, which protects against P. vivax infection. The out-of-Asia scenario, meanwhile, is supported by phylogenetic analyses of malaria parasites found among Asian monkeys.

By sequencing more than 400 P. vivax samples from different parts of the world and more than a dozen P. vivax-like­ samples, researchers led by Virginie Rougeron from the Laboratoire MIVEGEC in France characterized the genetic variation among the parasites. From this, they traced the likely origin of P. vivax to Southeast Asia and further found it likely spread through serial founder events, as they reported in Science Advances on Wednesday.

"A better understanding of the origin of P. vivax in population genomic gives us more fundamental new knowledge of the evolution of the pathogens," Rougeron said in an email. She added that that can, in turn, provide insight into where new mutations, including resistance mutations, could crop up rapidly. "[That] is very important today, knowing that no new treatment against malaria currently exists," she said.

Rougeron and her colleagues analyzed genome-wide data from 1,154 P. vivax isolates from 21 different countries, including 20 newly sequenced isolates from Mauritania, Ethiopia, and Sudan, and 27 P. vivax-like isolates. After quality control measures, the dataset included 447 P. vivax and 19 P. vivax-like samples. Within these, the researchers identified more than 2 million SNPs.

Using that SNP data, they constructed maximum likelihood genetic trees that revealed three distinct clades. The first separated the P. vivax and the P. vivax-like samples and showed them to be sister clades. This, the researchers noted, is in contrast to a previous analysis using single-gene phylogenies that suggested that P. vivax fell within the radiation of P. vivax-like.

The second split was among P. vivax-like strains themselves, which appeared to be made up of two different lineages. As these strains did not recombine, the researchers suggested they could represent separate species.

Further analyses with population genomics approaches and tools like principal components analysis, the Admixture algorithm, and F-statistics tools found consistent patterns among the P. vivax samples that clustered them by geographical location. This split Southeast Asian samples from the African and American ones. Samples from India and Sri Lanka were genetically closer to African samples than to other Asian ones, which the researchers noted could reflect human movements over the last few thousand years. The American strains further separated into two populations with different ancestral origins.

By modeling the shared and population-specific genetic drift, the researchers traced the most recent common ancestor of P. vivax to within populations from Southeast Asia. Additional analyses further suggested that P. vivax spread from that ancestral Southeast Asian population through a series of founder events all over the world.

Rougeron and her colleagues are now examining in particular how P. vivax spread to the Americas. There's question, she noted, whether it traveled there through the transatlantic slave trade or through other migrations from Europe or Asia.