South-East Asian strains of Plasmodium falciparum display 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 on Plasmodium falciparum strains from South-East Asia differ from African strains. We find a significantly higher ratio of non-synonymous to synonymous polymorphisms in P. falciparum from South-East Asia compared to Africa, suggesting differences in the selective constraints on P. falciparum genome 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.

Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa

“…45 The high ratio of nonsynonymous-to-synonymous substitutions among these protein coding genes (2.7 for Pow, 1.3 for Poc) is similar to that seen in P. falciparum and P. vivax. 46,47 This finding may represent diversifying selection on proteins across either P. ovale genome, enabling maintenance of nonsynonymous substitutions. The impact of the malaria life cycle on allele frequencies has also been observed to inflate dN/dS ratios among Plasmodium parasites.…”