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The division into the two subgenera (Leishmania and Viannia) was made by Lainson and Shaw in 1987 on the basis of their location within the insect gut. At least three subgenera exist: Leishmania, Sauroleishmania, and Viannia. One theory proposes an African origin, with migration to the Americas. Several of these genera may be polyphyletic and may need further division.

Depending on the stage of their lifecycle, they exist in two structural variants, as: The details of the evolution of this genus are debated, but Leishmania apparently evolved from an ancestral trypanosome lineage.The precise structure of lipophosphoglycan varies depending on the species and lifecycle stage of the parasite.The glycan component is particularly variable and different lipophosphoglycan variants can be used as a molecular marker for different lifecycle stages. The four genera Leptomonas, Crithidia, Leishmania, and Endotrypanum form the terminal branches, suggesting a relatively recent origin. Trypanosoma cruzi groups with trypanosomes from bats, South American mammals, and kangaroos suggest an origin in the Southern Hemisphere. The remaining clades in this tree are Blastocrithidia, Herpetomonas, and Phytomonas.

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