title: South-East Asian strains ofPlasmodium falciparumdisplay higher ratio of non-synonymous to synonymous polymorphisms compared to African strains.
abstract: Resistance to frontline anti-malarial drugs, including artemisinin, has repeatedly arisen in South-East Asia, but the reasons for this are not understood. Here we test whether evolutionary constraints onPlasmodium falciparumstrains from South-East Asia differ from African strains. We find a significantly higher ratio of non-synonymous to synonymous polymorphisms inP. falciparumfrom South-East Asia compared to Africa, suggesting differences in the selective constraints onP. falciparumgenome in these geographical regions. Furthermore, South-East Asian strains showed a higher proportion of non-synonymous polymorphism at conserved positions, suggesting reduced negative selection. There was a lower rate of mixed infection by multiple genotypes in samples from South-East Asia compared to Africa. We propose that a lower mixed infection rate in South-East Asia reduces intra-host competition between the parasite clones, reducing the efficiency of natural selection. This might increase the probability of fixation of fitness-reducing mutations including drug resistant ones.
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Gajinder Pal
authors.identifier: 0000-0002-3972-3324
authors.initials: GP
authors.lastname: Singh
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
keywords: Plasmodium falciparum; artemisinin resistance; non-synonymous polymorphism; resistance evolution