To the editor

In the March issue, Fiscella et al. (Nat. Biotechnol. 21, 302–307, 2003) identify a novel human T-cell immunomodulatory protein (TIP). Their study has direct relevance for massive BLAST searches that we have carried out at the DNA level to identify genes responsible for centriolar mitosis by fishing out genes present in animals and unicellular flagellates and not in other types of organisms. Among such genes we have found in the Plasmodium falciparum genome, which mostly encode proteins participating in construction of the flagella, there is also a homolog of TIP, annotated a 'hypothetical protein' Q8I3H7. Indeed, when a Smith-Watermann search is carried out using TIP as a query, this Plasmodium protein is found (with an expect value of 1.06E–108) as the only non-animal protein homologous to TIP. The two proteins share 29.6 % identical residues along the whole length. Analysis with SMART1 (http://smart.embl-heidelberg.de/) reveals that the TIP and Q8I3H7 also have a similar structure, both containing transmembrane domains.

Given the relatively low homology between the two proteins, as well as low homology between Plasmodium protein and its homolog from the natural mosquito vector (Anopheles gambiae and Plasmodium proteins share 25% identical residues), the possibility of recent horizontal gene transfer appears unlikely.

In this light, there are two possible explanations for the presence of a TIP homolog in the Plasmodium genome. Q8I3H7 may be an old secretory protein necessary for the Plasmodium lifecycle, further adapted to T-cell regulation. Alternatively, a very interesting possibility is that the TIP homolog is involved in P. falciparum's parasitic lifestyle and its ability to immunomodulate the host organism. T cells have been shown to play a major role in early stages in protective immunity against malaria parasites2. Analogous to the protective effect of TIP protein in graft-versus-host disease described by Fiscella et al., Q8I3H7 may protect the parasite against attack by the host immune system.