The LPG1 gene family of Leishmania major

In Leishmania major, the core of the abundant surface lipophosphoglycan (LPG) is structurally related to that of the smaller glycosylinositolphospholipids (GIPLs) in containing galactosylfuranose (Gal _f) residues in a Gal_f (β1, 3)Man motif. However, deletion of the putative Gal_f-transferase (Gal_fT) LPG1 affected Gal_f incorporation in LPG but not GIPLs. We hypothesized that the presumptive GIPL Gal_f-transferases could be homologous to LPG1, and identified three related genes in the L. major genome. These were termed LPG1L, LPG1R, and LPG1G, the latter of which was found in three identical copies located at the telomeres of chromosomes 5, 19, and 32 based on Leishmania genome project data. Neither LPG1 nor its homologues LPG1L and LPG1R were involved in the biosynthesis of GIPLs, as an lpg1^-/lpg1l ^-/lpg1r^- triple knockout (the first such in Leishmania) grew normally and made wild-type levels of Gal_f -containing GIPLs. In contrast, overexpression of these three led to elevated galactose incorporation in glycoproteins. Gal_f-containing glycoproteins had not been described in Leishmania but occur at high levels in other closely related trypanosomatids including Trypanosoma cruzi, Crithidia, Leptomonas, and Endotrypanum, and LPG1L and LPG1R homologs were detected in these species. These data suggest that the glyco-synthetic capabilities of Leishmania and perhaps other trypanosomatids may be larger than previously thought, with some activities being 'cryptic' in different lineages and potentially serving as reservoirs for glycoconjugate variation during evolution. Future tests will address whether the LPG1G family encodes the hypothesized GIPL-specific Gal _fT.