Abstract
BackgroundComparative genome analyses of parasites allow large scale investigation of selective pressures shaping their evolution. An acute limitation to such analysis of Plasmodium falciparum is that there is only very partial low-coverage genome sequence of the most closely related species, the chimpanzee parasite P. reichenowi. However, if orthologous genes have been under similar selective pressures throughout the Plasmodium genus then positive selection on the P. falciparum lineage might be predicted to some extent by analysis of other lineages.Principal FindingsHere, three independent pairs of closely related species in different sub-generic clades (P. falciparum and P. reichenowi; P. vivax and P. knowlesi; P. yoelii and P. berghei) were compared for a set of 43 candidate ligand genes considered likely to be under positive directional selection and a set of 102 control genes for which there was no selective hypothesis. The ratios of non-synonymous to synonymous substitutions (dN/dS) were significantly elevated in the candidate ligand genes compared to control genes in each of the three clades. However, the rank order correlation of dN/dS ratios for individual candidate genes was very low, less than the correlation for the control genes.SignificanceThe inability to predict positive selection on a gene in one lineage by identifying elevated dN/dS ratios in the orthologue within another lineage needs to be noted, as it reflects that adaptive mutations are generally rare events that lead to fixation in individual lineages. Thus it is essential to complete the genome sequences of particular species of phylogenetic importance, such as P. reichenowi.
Highlights
Identifying genes under positive directional selection can help understand how parasites adapt to new survival or reproductive challenges
Could the results of that analysis be extrapolated to P. falciparum genes for which P. reichenowi orthologous sequences are not available? This study tests whether signatures from one clade of the Plasmodium genus can be used to predict those in other clades
For each of the 43 candidate ligand genes analysed, interspecific dN/dS ratios are shown for each of the three closely related species pairs, P. falciparum / P. reichenowi, P. vivax / P. knowlesi, and P. yoelii / P. berghei (Table 1, further details in table S1). To test whether this candidate ligand gene dataset is enriched in genes under positive selection, dN/dS values were compared with the control gene dataset for each species pair (Fig. 1A) using Wilcoxon’s rank sum test
Summary
Identifying genes under positive directional selection can help understand how parasites adapt to new survival or reproductive challenges. Pairwise analyses with other malaria parasite species may identify loci under positive selection. Analyses of closely related species are preferable, and pairwise dN/dS analysis among the genomes of the rodent malaria parasites, P. yoelii, P. berghei and P. chabaudi [7], showed a similar overall trend to the falciparumreichenowi analysis, with putative membrane proteins displaying higher dN/dS values than other genes.
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