Factors influencing the global distribution pattern and diversity of Plasmodium vivax malaria (Pv) are increasingly better understood, but often separated by research focusing only on specific type (drug resistance, geography, migration) and/or region (East Africa, South America, Thailand). Studying only part of the bigger picture can lead to misinterpretation or neglect of interactions that enhance or dampen patterns observed. We studied Pv mitochondrial genome (mtDNA) differentiation across the eastern hemisphere in relation to three influencing factors: human migratory movements, mosquito vector species, and geography.
We sequenced the mtDNA from >200 Pv samples from patients in Melanesia, Vanuatu, Uzbekistan, Armenia, Azerbaijan and Sudan using Sanger sequencing. The data was supplemented with data available from previous publications, to >800 samples from 41 countries. Phylogenetic connections and age estimates were generated with the use of Bayesian phylogenetics programme BEAST2, and data processed further through PCA, DAPC and general population genetic measures. Comparisons were made between the Pv mtDNA, human genome, major mosquito vector species and geographic variables.
Results indicate that besides each independent factor influencing patterns of distribution, interactions are of clear additional interest. We see evidence of the earliest human migrations from over 100.000 years ago introducing malaria into different geographic regions. Vector species differences and geography either maintained and enhanced this pattern, or reduced it. Specifically in the east, varying mosquito vector species between geographic regions (e.g. Myanmar, China, Melanesia) formed a barrier to colonisation by new Pv strains. Combined with relatively low levels of human migration, this interaction has probably maintained differences in the mtDNA as introduced by ancient human migrations.
We show that studying interactions between factors influencing evolution and distribution helps explain genetic patterns that cannot be understood in terms of individual causal variables.