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PROTEINS INVOLVED IN THE BIOSYNTHESIS OF LIPOPHOSPHOGLYCAN IN LEISHMANIA: A COMPARATIVE GENOMIC AND EVOLUTIONARY ANALYSIS
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Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Programa de Pós-Graduação em Biotecnologia e Medicina Investigativa. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Programa de Pós-Graduação em Biotecnologia e Medicina Investigativa. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Programa de Pós-Graduação em Biotecnologia e Medicina Investigativa. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Programa de Pós-Graduação em Biotecnologia e Medicina Investigativa. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Programa de Pós-Graduação em Biotecnologia e Medicina Investigativa. Salvador, BA, Brasil.
Resumen en ingles
Leishmania spp. are digenetic parasites capable of infecting humans and causing a range of diseases collectively known as leishmaniasis. The main mechanisms involved in the development and permanence of this pathology are linked to evasion of the immune response. Crosstalk between the immune system and particularities of each pathogenic species is associated with diverse disease manifestations. Lipophosphoglycan (LPG), one of the most important molecules present on the surface of Leishmania parasites, is divided into four regions with high molecular variability. Although LPG plays an important role in host-pathogen and vector-parasite interactions, the distribution and phylogenetic relatedness of the genes responsible for its synthesis remain poorly explored. The recent availability of full genomes and transcriptomes of Leishmania parasites offers an opportunity to leverage insight on how LPG-related genes are distributed and expressed by these pathogens. Results: Using a phylogenomics-based framework, we identified a catalog of genes involved in LPG biosynthesis
across 22 species of Leishmania from the subgenera Viannia and Leishmania, as well as 5 non-Leishmania trypanosomatids.
The evolutionary relationships of these genes across species were also evaluated. Nine genes related to
the production of the glycosylphosphatidylinositol (GPI)-anchor were highly conserved among compared species,
whereas 22 genes related to the synthesis of the repeat unit presented variable conservation. Extensive gain/loss
events were verified, particularly in genes SCG1-4 and SCA1-2. These genes act, respectively, on the synthesis of the
side chain attached to phosphoglycans and in the transfer of arabinose residues. Phylogenetic analyses disclosed
evolutionary patterns reflective of differences in host specialization, geographic origin and disease manifestation.
Conclusions: The multiple gene gain/loss events identified by genomic data mining help to explain some of the
observed intra- and interspecies variation in LPG structure. Collectively, our results provide a comprehensive catalog
that details how LPG-related genes evolved in the Leishmania parasite specialization process.
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