NEW YORK (GenomeWeb News) – Malaria-related resistance has evolved similarly in humans and wild primates, according to a newly published study of baboons in East Africa.
Researchers from Duke University and the National Museums of Kenya's Institute of Primate Research used gene sequencing and gene expression studies to try to get to the bottom of primate resistance to a malaria-like parasite called Hepatocystis. After evaluating DNA and expression patterns in the blood of yellow baboons in Kenya and Tanzania, the team concluded that a genetic variant mediating Hepatocystis resistance in baboons has similar effects as a variant governing some types of malaria resistance in humans. The research appeared online today in Nature.
"It's a nice example of how — in the vastness of the genome — the same gene was modified in the same way in two different species to produce the same kind of resistance," senior author Gregory Wray, director of Duke University's Institute for Genome Sciences and Policy, said in a statement. "That's a pretty remarkable thing when you think of all of the different ways malaria resistance might have evolved."
In humans, malaria is caused by the Plasmodium vivax parasite or related Plasmodium species. Not everyone is equally susceptible to malaria, though. Differences in human susceptibility to P. vivax and knowlesi parasites arise from differences in the regulation of a gene called FY or DARC, which codes for a chemokine receptor on the surface of red blood cells.
Past research suggests a change from a thymine to cytosine nucleotide in an FY regulatory region curtails the gene's expression and protects individuals from P. vivax or P. knowlesi infection. The C variant has popped up at least twice in human populations — once in Africa and independently in Papua New Guinea.
In contrast to humans, wild baboons aren't usually infected with malaria parasites. But they are prone to infection by a related parasite, Hepatocystis, which is transmitted from one primate to the next by biting midges.
"The unusual evolutionary history of this locus led us to investigate the pattern of genetic variation in its baboon homologue," they wrote, "and to explore the possibility that it might also explain phenotypic variation in parasite infection in a wild primate population."
To test this, the researchers looked at both Hepatocystis infection patterns and genetic variation at the FY gene in 190 baboons from Kenya's Amboseli National Park.
The team found that nearly 62 percent of the baboons tested had Hepatocystis parasites in their blood. Even so, the infection rates varied both within and outside the park. Samples from ten baboons at the Masai Mara Reserve, also in Kenya, indicated that infection rates were just 30 percent at that park. On the other hand, 90 percent of the 20 baboons tested at Tanzania's Mikumi National Park were infected with Hepatocystis.
Next, the researchers isolated DNA from 174 baboon blood samples and sequenced the region homologous to the human malaria-related FY regulatory region. Using this approach, they found six SNPs in the baboon FY regulatory region. Of these, one adenine/guanine variant was significantly associated with Hepatocystis infection.
The site of the T to C SNP affecting malaria susceptibility in humans did not vary in the baboons tested. Nevertheless, the team's gene expression experiments indicated that the A/G variant in baboons had the same effect on FY gene expression as the C/T variant in humans, with A alleles decreasing FY expression in baboons and G alleles increasing it.
"In spite of the parallels that we have documented for baboon and human FY, the functional variants we have identified in baboons are not homologous to the known functional variant in humans," the researchers wrote, "which reveals that phenotypic variation in different primate species may show similar, but not precisely convergent, patterns of evolution."
In the future, the researchers argue, such insights may not only provide new clues about the way environmental factors shape variation in primate genomes, but could also explain some aspects of human biology.