Genetic mapping of fitness determinants across the malaria parasite   < i > Plasmodium falciparum < /i > life cycle

by Xue Li, Sudhir Kumar, Marina McDew-White, Meseret Haile, Ian H. Cheeseman, Scott Emrich, Katie Button-Simons, Fran çois Nosten, Stefan H. I. Kappe, Michael T. Ferdig, Tim J. C. Anderson, Ashley M. Vaughan Determining the genetic basis of fitness is central to understanding evolution and transmission of microbial pathogens. In human malaria parasites (Plasmodium falciparum), most experimental work on fitness has focused on asexual blood stage parasites, because this stage can be easily cultured, although the transmission of malaria requires both femaleAnopheles mosquitoes and vertebrate hosts. We explore a powerful approach to identify the genetic determinants of parasite fitness across both invertebrate and vertebrate life-cycle stages ofP.falciparum. This combines experimental genetic crosses using humanized mice, with selective whole genome amplification and pooled sequencing to determine genome-wide allele frequencies and identify genomic regions under selection across multiple lifecycle stages. We applied this approach to genetic crosses between artemisinin resistant (ART-R,kelch13-C580Y) and ART-sensitive (ART-S,kelch13-WT) parasites, recently isolated from Southeast Asian patients. Two striking results emerge: we observed (i) a strong genome-wide skew (>80%) towards alleles from the ART-R parent in the mosquito stage, that dropped to ~50% in the blood stage as selfed ART-R parasites were selected against; and (ii) repeatable allele specific skews in blood stage par...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research