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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.

South-East Asian strains of Plasmodium falciparum display higher ratio of non-synonymous to synonymous polymorphisms compared to African strains