FORS-D is a measure of the contribution of base order to the stem loop potential of a nucleic acid sequence and can also give information on evolutionary pressures on sequences to move away from secondary structure. Negative FORS-D values in a gene are associated with exons and nucleotide substitutions such as SNPs. An analysis of P. falciparum genes under selection pressure shows a correlation between negative FORS-D values and SNP density for genes that drug targets but not for drug transporters or antigenic variation genes. Analysis of the dhfr gene shows that a majority of rare mutations that associate with drug resistance also fall into regions with negative FORS-D values. These data suggest that FORS-D values might be predictors for drug target genes and drug resistance mutations in these genes.
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