These observations are in agreement with the classification obtained by Inoue et al. using the binary topology pattern methodology for the lengths of loops and tails of serpentine receptors, where PfSR1 was classified as a member of Class C, and PfSR10 and PfSR25 as members of Class A. PfSR12 was included in the Inoue et al. analysis as the FullPhat automatic gene prediction ; in fact, this gene prediction is probably a composition of two distinct genes, a helicase and the heptahelical receptor PfSR12, which were correctly separated at the final PlasmoDB annotation. In conclusion, in spite of the absence of amino acid sequence similarity with well-characterized serpentine receptors, the P. falciparum serpentine receptor-like proteins show Tasocitinib overall 7-TM architectures that resemble the ones exhibited by members belonging to different families of serpentine receptors. We next investigated the presence of serpentine receptor-like homologues in other Plasmodium species. The amino acid sequences of PfSRs were used to scan the genome sequences from two other primate parasites and from three rodent parasites. Most of the tBLASTn searches retrieved parasite sequences that are truncated or not annotated. Comparative gene-finding methods have proved to be powerful tools to assign gene function for related organisms. In order to identify more reliable gene structures for the PfSR homologues, we performed a homology-based gene prediction using the program FGENESH+, which is one of the most accurate programs available at the moment and is also trained to predict intron splice sites in P. falciparum. We recomputed gene predictions from genomic regions of other Plasmodium species containing predicted exons with significant protein similarity to the PfSRs by using FGENESH+. However, it is important to mention that in the case of determining the gene structure of pfsr12 orthologues in other Plasmodium species we had to manually inspect and correct the predictions of introns/exons. Since we had amplified the full-length of pfsr12 by RT-PCR and PI-103 sequenced it, we were certain about its intron-exon gene structure; with this knowledge in conjunction with analysis using FGENESH+ and the algorithm for homology comparison ��BLAST 2 sequences��, we were able to identify the most reliable gene predictions. Finally, we analyzed the synteny maps provided by PlasmoDB to confirm the orthology of these genes. Predicted protein and nucleotide sequences as well as alignments of Plasmodium serpentine receptor homologues and for phylogenetic tree building are available in Data S1, S2, S3, S4. The P. falciparum genome is completely sequenced, the P. yoelii genome is extensively sequenced, and currently a large number of genomic sequences from other Plasmodium species is also available.