Vacuolar H+-Pyrophosphatase


Trypanosomatids and apicomplexans contain subcellular organelles, rich in calcium and pyrophosphate, which are called acidocalcisomes (Scott et al, 1998; Docampo and Moreno, 2001). These organelles share properties with the vacuoles of plants and they all are characterized by the presence in their membranes of two proton pumps, a vacuolar H+-ATPase, and a vacuolar H+-pyrophosphatase (V-PPase). The V-PPase is an enzyme previously described only in plants and bacteria but a recent phylogenetic analysis carried out with the homologous sequences revealed that three available trypanosomatid sequences were monophyletic with the sequences of the apicomplexans P. falciparum and Toxoplasma gondii. Moreover, all the above protists formed a single clade of type-I V-PPases together with the green algae Chlamydomonas reinhardtii and Chara corallina and with plants (see also Drozdowicz and Rea, 2001) .

 

Further details of the analysis


A Trypanosoma cruzi vacuolar H+-dependent pyrophosphatase (VHPPASE)( Q9NDF0 ) was compared with all the sequences of the Trembl/SwissProt database indexed at European Bioinformatics Institute (EBI, Hinxton UK), using the NCBI BLASTP program and the BLOSUM 62 matrix (http://www2.ebi.ac.uk/blastall/). Click here to inspect the BLASTP output file. The best scoring sequences after that of T. cruzi were those of the plant VHPPASEs and those of Chlamydomonas reinhardtii (CAC44451) and Toxoplasma gondii (Q9BK07), an incomplete sequence of Leishmania major (Q9GVF8)and Plasmodium falciparum (O97154) (scores ranging from 779-622, or E=0 - e-177). The best scoring sequences (E values of 0 to 1e-12 ) were selected for the creation of an alignment by Clustal. The alignment was freed of duplicate and incomplete sequences and gaps and the resulting alignment of 31 sequences with 546 sites was used for further analyses. The program Clustal was used to calculate a table with uncorrected pairwise distances. Pairwise percentages of identity of the T. cruzi sequence with that of the plants, including the chlorophyte alga Chlamydomonas reinhardtii was 58-56%, while the sequences of Toxoplasma and Plasmodium shared between 50% identical residues. All other sequences shared 44-35% identical residues.

The alignment in Phylip format was used for likelihood mapping as implemented in PUZZLE version 4.0.1. The result indicated that the dataset contained a strong phylogenetic signal with 95.5% of the quartets fully resolved and only 2.5% of all quartets that were unresolved.

A bootstrapped neigbor-joining tree (1000 bootstrap samplings), a maximum likelihood (10 000 puzzling steps) and a bootstrapped maximal parsimony tree (100 bootstrap samplings) were created using the alignment in Phylip format. All three trees were robust and clustered the trypanosomatid sequence together with that of Toxoplasma, and Plasmodium. In the NJ tree T. cruzi was paraphyletic with the other two protists, while in the ML and MP trees all three protists behaved as a monophyletic group. Clustering together with the plants and the two chlorophyte alga received 100 % support in all three phylogenetic inference methods.

Conclusion


The trypanosome VHPPASE is robustly monophyletic with the plant and the Apicomplexan VHPPASEs. Support for this comes from three phylogenetic inference methods and distance data.