Mitotic Evolution of Plasmodium falciparum Shows a Stable Core Genome but Recombination in Antigen Families

摘要: Malaria parasites elude eradication attempts both within the human host and across nations. At individual level, evade immune responses through antigenic variation. global escape drug pressure single nucleotide variants gene copy amplification events conferring resistance. Despite their importance to health, rates at which these genomic alterations emerge have not been determined. We studied complete genomes of different Plasmodium falciparum clones that had propagated asexually over one year in presence absence pressure. A combination whole-genome microarray analysis next-generation deep resequencing (totaling 14 terabases) revealed a stable core genome with only 38 novel appearing seventeen evolved (avg. 5.4 per clone). In exposed atovaquone, we found cytochrome b mutations as well an event encompassing P. multidrug resistance associated protein (mrp1) on chromosome 1. observed 18 large-scale (>1 kb average) deletions telomere-proximal regions encoding multigene families, involved evasion (9.5×10−6 structural base pair generation). Six were chromosomal crossovers generated during mitosis. minor differences between genetically distinct strains cultured or drug. Using derived mutation for (1.0–9.7×10−9 generation), can now model frequency alleles will under well-defined set assumptions. Further, detection mitotic recombination var families illustrates how arise change time falciparum. These results help improve our understanding evolves control efforts hosts large populations.