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Author for correspondence: Olof Hellgren, Email: [email protected]
Introduction
When organisms evolve a parasitic life strategy, this often results in gene losses and size reduction of the genomes (Tamas et al. 2001; Sakharkar et al. 2007; Lee and Marx, 2012). This is mainly because parasites utilize metabolites and proteins from their hosts, making some metabolic machineries redundant (Kemen et al. 2011). However, different host–parasite combinations and life history traits will cause the loss of different genes and pathways, and in some cases parasites might even acquire or evolve new metabolic pathways to complement those of its host (Pombert et al. 2012).
In most organisms, thiamine (vitamin B1) acts as an essential co-factor for several enzymes involved in carbohydrate and amino acid metabolism. Fungi, bacteria and plants can synthesize thiamine de novo, whereas most other organisms must salvage it from external sources.
De novo synthesis of thiamine requires enzymes that produce two essential moieties [4-amino-2-methyl-5-diphosphomethylpyrimidine and 4-methyl-5-(2-phosphoethyl)-thiazole), as well as an enzyme that combines these moieties into thiamine monophosphate (Helliwell et al. 2013, Fig. 1). In the primate malaria parasites, Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi, the genes coding for these three key enzymes (hydroxyethylthiazole kinase ThiM, hydroxymethylpyrimidine kinase ThiD and thiamine-phosphate diphosphorylase ThiE) have been found (Frech and Chen, 2011). Further, in P. falciparum, the proteins coded by the genes ThiM, ThiD and ThiE have been shown experimentally to exhibit the expected enzymatic functions in the thiamine pathway (Wrenger et al. 2006). However, these enzymes have been shown to be absent in the rodent malaria parasites (Plasmodium berghei, Plasmodium chabaudi and Plasmodium yoelii) (Frech and Chen, 2011). Likewise, in the sequenced genomes of apicomplexan parasites more distantly related to malaria parasites (i.e. Theileria, Babesia, Toxoplasma spp., Neospora spp., Eimeria spp. and Cryptosporidia spp.), none of the required enzymes for this de novo synthesis have been found (Müller and Kappes, 2007; Shanmugasundram et al. 2013). Although thiamine is essential for survival (Helliwell et al. 2013), loss of this pathway leads to thiamine auxotrophy (i.e. vitamin dependence from an external source) and has occurred repeatedly in the course of evolution in eukaryotes, suggesting a trade-off in the cost of synthesizing the vitamin against the probability...