Research Project
8080434
DESCRIPTION (provided by applicant): The purpose of this research is to characterize the genetic structure and transmission dynamics of the human malaria parasite Plasmodium vivax, with the long-term goal of understanding the evolutionary biology of this species and its potential implications for malaria treatment and control. Plasmodium vivax is associated with 70-80 million clinical cases of malaria reported each year, with 2.6 billion people at risk of infection worldwide. Institutions based in two P. vivax-endemic countries, Brazil and Sri Lanka, are partnering with leading research groups in the USA to address the following specific research aims: 1) To estimate levels of microsatellite diversity, single-nucleotide polymorphism (SNP) density and recombination rates and to examine the geographic structure of worldwide populations of P. vivax;2) To examine the transmission dynamics of genetically distinct P. vivax strains in a well-characterized cohort of malaria-exposed subjects and determine the rate at which new haplotypes are introduced or disappear in the population;3) To carry out SNP and microsatellite discovery across a 300-kb chromosome segment of four representative strains of P. vivax and to standardize high-throughput strategies for large-scale typing of these SNPs in field isolates;4) To compare these 300-kb of DNA sequence of P. vivax with the corresponding sequence in one of its closest relatives, the monkey malaria parasite P. knowlesi, to obtain estimates of single-nucleotide mutation rates and SNP density for various types of DNA sequence (microsatellite repeats vs. complex sequences, coding vs. noncoding DNA) of P. vivax and to allow the identification of genes under positive selection across this chromosome segment. This in-depth analysis of the mechanisms that create and maintain genetic variation in this human malaria parasite will provide crucial information to predict how fast novel phenotypes of public health importance, such as drug resistance and new antigenic variants, originate and spread in natural populations of P. vivax. In addition, the estimates of recombination rates in different parasite populations, to be generated by the chromosome-wide analysis of informative microsatellite and SNP loci in field-collected isolates, facilitate the design of genome-wide association mapping studies to identify genes that are responsible for important parasite traits in diverse epidemiological settings.
