More than one way to build a flagellum: comparative genomics of parasitic protozoa

The membrane bound, microtubular axonemes of eukaryotic cilia and flagella are assembled at their distal tips. The discovery of intraflagellar transport (IFT) in Chlamydomonas provided an exciting and seemingly unifying framework for the formation of all eukaryotic cilia and flagella [1–3]. IFT operates in the space between the axoneme and the flagellar membrane to move particles from and to the cytoplasmic basal body and the assembly at the distal tip site. Anterograde movement is conducted via a kinesin II microtubule motor and retrograde movement via a specific IFT dynein. The particle cargo is likely to be a variety of proteins involved in axoneme structure and assembly and there is evidence that the basal body transitional fibres, which link the basal body to the membrane, act as docking sites for IFT particles [2,4]. The IFT system has been widely conserved in evolution and IFT mutations produce particular and medically relevant pathologies [3,5]. Recently the genomes of a number of parasitic protozoa have been sequenced. These organisms exhibit interesting variations in flagellum biology [6]. We employed the publicly available IFT protein sequences in bioinformatic interrogations for the signature of the IFT system in these genomes. We included flagellates, such as Giardia, kinetoplastid parasites (causing sleeping sickness, leishmaniasis and Chagas disease), and a range of apicomplexan parasites (such as those causing malaria, toxoplasmosis and coccidiosis). We detected genes encoding the IFT particle proteins, the kinesin II and IFT dynein motors in the genome of Trypanosoma brucei and two other kinetoplastid parasites, Leishmania major and T. cruzi. We also detected IFT particle genes in Giardia. However, we noted the apparent complete absence of IFT genes in the completed genome of the malarial parasite Plasmodium falciparum. This apicomplexan produces a flagellated microgamete and might thus be expected to possess at least some IFT components [6]. We, therefore, analysed all available apicomplexan parasite genomes for the presence of IFT genes. Using homology searches with full-length IFT protein sequences and short, highly conserved regions we reiteratively interrogated the genomes of Eimeria, Toxoplasma, Plasmodium, Cryptosporidium and Theileria. We identified IFT particle and the IFT kinesin II sequences in the partially sequenced Toxoplasma genome and found an IFT signature in Eimeria. However, there were no IFT genes in the genomes of the malarial parasites P. falciparum, Cryptosporidium or two Theileria species. As a control, we searched for conserved cytoskeletal proteins, including δ δ-tubulin [7] and PF16 [8], which are …