MULTIGENIC DRUG-RESISTANCE AMONG INBRED MALARIA PARASITES

Recent population genetic studies on the malaria parasite Plasmodium f alciparum have confirmed that selfing is more frequent where the trans mission rate is lower; with inbreeding coefficients estimated to be 0. 33 and 0.92 for sites in Tanzania and Papua New Guinea (PNG), respecti vely. These geographical differences in Plasmodium mating patterns hav e been linked to the rate of spread of chloroquine resistance (CQR) wh ich, according to some measures, has been slower in Tanzania than in P NG. It has been proposed that the former observation explains the latt er, although the theoretical argument linking the two is based on limi ted simulation studies. Taking a more analytical approach here, we fir st establish the relevant relationship between the coefficient of inbr eeding (F, within loci) and the recombination race (r, between loci), defining an 'effective recombination rate', (r) over tilde = r-(1-F). We then show that the em of multigenic drug resistance can indeed be s lowed (or even quickened) by more outcrossing, but only when resistanc e is determined by two or more genes, none of which independently conf ers significant protection. The resistance genes should both be initia lly rare, and subject to low selection pressure. The analysis does not completely discount the hypothesis that inbreeding significantly infl uences the spread of CQR, but we show that it can only do so under a r estrictive set of conditions, and that these conditions are not satisf ied by some laboratory and field data. We discuss some of the wider im plications of these results for the evolution of multigenic resistance .