Mutation rates in the dihydrofolate reductase gene of Plasmodium falciparum.

摘要: A new method has been established to define the limits on a spontaneous mutation rate for gene in Plasmodium falciparum. The combines mathematical modelling and large-scale vitro culturing calculates difference mutant frequencies at 2 separate time-points. We measured positions dihydrofolate reductase (DHFR) of 3D7, pyrimethamine-sensitive line P. This was re-cloned an effectively large population treated with selective pyrimethamine concentration 40 nM. detected point mutations codon-46 (TTA TCA) codon-108 (AGC AAC), resulting serine replacing leucine asparagine respectively corresponding product. substitutions caused decrease sensitivity. By we determined that given position DHFR low occurred less than 2.5 x 10(-9) mutations/DHFR gene/replication. result important implications genetic diversity antimalarial drug therapy by demonstrating even rates anti-malarial resistance will inevitably arise when alleles are selected under pressure.