Evolutionary History and Biogeography of Leishmania: An Integrative Phylogenomic, Molecular, Host–Vector, and Viral Framework

The evolutionary origin and global diversification of Leishmania remain unresolved, with competing biogeographic hypotheses proposing Neotropical, Nearctic, or Palearctic origins. This narrative review integrates phylogenomic, molecular, biochemical, ecological, biogeographic, and host–vector evidence to critically examine the evolutionary history of the genus and the processes underlying its diversification and contemporary distribution. Particular emphasis is placed on the evolutionary relationships among major Leishmania lineages, host and vector associations, the diversification of the subgenus Mundinia, and the limitations of geography-centered models in explaining the observed phylogenetic and biogeographic patterns. Comparative evidence indicates that no single geographic hypothesis adequately accounts for the combined patterns of lineage diversification, host-switching, vector adaptation, intercontinental dispersal, and ecological specialization observed across the genus. The review therefore develops an integrative framework in which paleogeography is considered together with parasite evolution, host–vector interactions, and persistent viral associations. Within this framework, we propose the Trojan Horse Viral Hypothesis, a testable conceptual model in which persistent viral endosymbiosis may have acted as an evolutionary facilitator during transitions across ecological, host, and vector boundaries. A specific prediction of this model is that viral acquisition or diversification should precede or coincide with major episodes of host or vector switching and parasite diversification; alternatively, viral associations that consistently arise only after host–vector specialization would argue against a causal facilitating role. The hypothesis is complemented by a Hidden Vector Scenario, which considers the possibility that ancestral transmission involved non-phlebotomine or extinct arthropod vectors that are no longer represented in contemporary transmission cycles. These propositions are explicitly presented as hypotheses rather than established historical mechanisms and generate testable predictions involving comparative phylogenomics, viromics, vector competence, host-range analyses, and molecular-clock approaches.