Sokoine University of Agriculture

Reduced variatio around drug-resistant dhfr alleles in African plasmodium falciparum

Show simple item record Pearce, Richard J Malisa, Allen L Kachur, Patrick Barnes, Karen Brian, Sharp Roper, Cally 2016-11-30T10:23:27Z 2016-11-30T10:23:27Z 2005-05-25
dc.description.abstract We have measured microsatellite diversity at 26 markers around the dhfr gene in pyrimethamine-sensitive and -resistant parasites collected in southeast Africa. Through direct comparison with diversity on sensitive chromosomes we have found significant loss of diversity across a region of 70 kb around the most highly resistant allele which is evidence of a selective sweep attributable to selection through widespread use of pyrimethamine (in combination with sulfadoxine) as treatment for malaria. Retrospective analysis through four years of direct and continuous selection from use of sulfadoxinepyrimethamine as first-line malaria treatment on a Plasmodium falciparum population in KwaZulu Natal, South Africa, has revealed how recombination significantly narrowed the margins of the selective sweep over time. A deterministic model incorporating selection coefficients measured during the same interval indicates that the transition was toward a state of recombination-selection equilibrium. We compared loss of diversity around the same resistance allele in two populations at either extreme of the range of entomological inoculation rates (EIRs), namely, under one infective bite per year in Mpumalanga, South Africa, and more than one per day in southern Tanzania. EIRs determine effective recombination rates and are expected to profoundly influence the dimensions of the selective sweep. Surprisingly, the dimensions were broadly consistent across both populations. We conclude that despite different recombination rates and contrasting drug selection histories in neighboring countries, the region-wide movement of resistant parasites has played a key role in the establishment of resistance in these populations and the dimensions of the selective sweep are dominated by the influence of high initial starting frequencies. en_US
dc.language.iso en en_US
dc.publisher Oxford University Press en_US
dc.subject Plasmodium falciparum en_US
dc.subject Selective sweeps en_US
dc.subject Pyrimethamine resistance en_US
dc.subject African en_US
dc.title Reduced variatio around drug-resistant dhfr alleles in African plasmodium falciparum en_US
dc.type Article en_US
dc.url DOI: 10.1093/molbev/msi177 en_US

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