Abstract
The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75) from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years) and long-term population history (79,235 to 104,008) of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes) to that inferred from mitochondrial genome diversity.
Highlights
Plasmodium vivax is the most prevalent malaria species outside Africa, causing widespread morbidity that can be severe and fatal [1,2,3,4,5,6]
P. vivax is distantly related to the more virulent Plasmodium falciparum, as inferred from mitochondrial and nuclear DNA variation [8,9,10,11]; the former appears to have evolved from a monkey malaria parasite between 20–35 million years ago via host switching [12]
We developed a panel of novel molecular markers including housekeeping genes, minisatellites and microsatellites to infer the evolutionary history of P. vivax on the Indian subcontinent
Summary
Plasmodium vivax is the most prevalent malaria species outside Africa, causing widespread morbidity that can be severe and fatal [1,2,3,4,5,6]. Various studies on the age and origin of extant P. vivax strongly support it as an ancient human malaria parasite that evolved in Southeast Asia [12,13,14,15]. Single nucleotide polymorphisms (SNPs) have been used by several researchers to elucidate the population history of P. falciparum and P. vivax [12,16,17,18]. These studies established the importance of using selectively neutral loci for determining the molecular age, origin, and evolutionary history of the parasites, assuming a ‘‘molecular clock’’ hypothesis. Genome sequencing of P. vivax has revealed a higher SNP density [22] and fewer microsatellite markers than in P. falciparum [23,24]
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