The Leishmania metaphylome: a comprehensive survey of Leishmania protein phylogenetic relationships

Background. Leishmaniasis is a neglected parasitic disease with diverse clinical manifestations and a complex epidemiology. It has been shown that its parasite-related traits vary between species and that they modulate infectivity, pathogenicity, and virulence. However, understanding of the species-specific adaptations responsible for these features and their evolutionary background is limited. To improve our knowledge regarding the parasite biology and adaptation mechanisms of different Leishmania species, we conducted a proteome-wide phylogenomic analysis to gain insights into Leishmania evolution./nResults. The analysis of the reconstructed phylomes (totaling 45,918 phylogenies) allowed us to detect genes that are shared in pathogenic Leishmania species, such as calpain-like cysteine peptidases and 3'a2rel-related proteins, or genes that could be associated with visceral or cutaneous development. This analysis also established the phylogenetic relationship of several hypothetical proteins whose roles remain to be characterized. Our findings demonstrated that gene duplication constitutes an important evolutionary force in Leishmania, acting on protein families that mediate host-parasite interactions, such as amastins, GP63 metallopeptidases, cathepsin L-like proteases, and our methods permitted a deeper analysis of their phylogenetic relationships./nConclusions. Our results highlight the importance of proteome wide phylogenetic analyses to detect adaptation and evolutionary processes in different organisms and underscore the need to characterize the role of expanded and species-specific proteins in the context of Leishmania evolution by providing a framework for the phylogenetic relationships of Leishmania proteins.We thank Leszek P. Pryszcz for his assistance with MetaPhOrs. DB group is funded by The National Institute of Science and Technology for Vaccines (Brazil) (MCT/CNPq, grant CNPq 573547/2008-4), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, grant # APQ-04073-10, PPM-00219-13) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES, grant # 051/2013). TG group research is funded in part by a grant from the Spanish ministry of Economy and Competitiveness (BIO2012-37161), a Grant from the Qatar National Research Fund grant (NPRP 5-298-3-086), and a grant from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC (Grant Agreement n. ERC-2012-StG-310325). GO group was funded by NIH-Fogarty (TW007012), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (REDE-56/11, RED-00014-14) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (309312/2012-4)