Amino acid sequence constraint and gene expression pattern across the life history in the malaria parasite Plasmodium falciparum

The relationship between gene expression across the life cycle and protein conservation in Plasmodium falciparum was examined by comparing gene expression data for six life-history stages with the number of nonsynonymous substitutions per site (dN) between 901 orthologous gene pairs of P. falciparum and Plasmodium yoelii. A high level of expression across the life history was associated with decreased dN and thus with protein conservation. By contrast, differential expression in the sporozoite and merozoite stages was associated with increased dN. At least some sporozoite- and merozoite-expressed genes with high dN have probably been subject to positive selection arising from parasite-host coevolution. A high level of expression across the life history was associated with higher than average G + C content at the first and second codon positions, whereas a high level of expression in the sporozoite and merozoite was associated with reduced G + C content at the first and second codon positions, the latter pattern evidently reflecting the relaxation of constraint on the amino acid sequence.