NIH funded project is undertaken
in collaboration with Dr. Gerald
Mkoji of the Kenya
Medical Research Institute (KEMRI), Nairobi, Kenya.
Other recent studies suggest we are still fundamentally ignorant about how, when and where S. mansoni and its snail hosts have evolved and diversified. We also lack a clear understanding of how the changing biogeography of S. mansoni will influence the degree of genetic diversity in this species, and how this diversity is apportioned within and among continents. One of the keys to understanding schistosome biology is to understand their obligatory relationships with snails. Presently, we lack even rudimentary information about the phylogenetic relationships of most schistosome-transmitting snails, and how that might have influenced schistosome evolution.
Modern molecular phylogenetic techniques offer a powerful way to address these fundamental questions. Such techniques have never been applied to a comprehensive series of samples representing the entire geographic range of S. mansoni or of any other human schistosome. We lack modern phylogenies for most of the molluscan hosts of African, Asian and American schistosomes and there has been no attempt to relate the variation inherent in S. mansoni with variation in its African and Neotropical molluscan hosts. Application of modern phylogenetic methods to a comprehensive sample of schistosomes and snails will provide a much clearer and long-overdue picture of how S. mansoni has evolved and continues to evolve. These insights will provide a new context in which to interpret all aspects of S. mansoni biology, including drug or vaccine responsiveness.
In collaboration with Dr. Mkoji we will be addressing several questions organized around two general topics:
1. Past and Present Evolution of S. mansoni:
Achieving a Global Perspective: With the assistance of a network of colleagues in several different countries, we will sample several S. mansoni populations to provide, for the first time, representative coverage of the geographic range of the species. Using automated sequencing techniques, relevant nuclear and mitochondrial gene sequences will be obtained and used to address the following questions:A. Are significant regional variants observed across the broad range of this species? Or do other factors such as human migration prevent such variation from occurring?
B. If significant intraspecific variation is observed, can it be correlated with geographical isolation or does coevolution with the molluscan or mammalian host act to perpetuate genetic variability within this species? For example, is a phylogenetic tree depicting relationships among S. mansoni populations congruent with trees showing relationships among Biomphalaria species or populations within widespread Biomphalaria species?
C. How has colonization of the Neotropics affected S. mansoni? Has this lead to increased diversification, including even incipient speciation, in the Neotropics?
D. What factors influence diversity within S. mansoni populations? Samples of S. mansoni populations from mainland or island sources, from low or high prevalence areas, or that differ with respect to past exposure to praziquantel or in diversity of available snail or mammalian host species will be compared in this regard.
2. Origins and Diversification of Biomphalaria and Implications for Schistosome Evolution:
Using the same network of colleagues, a comprehensive series of samples will be obtained of both African and Neotropical species of Biomphalaria and related planorbid snails that play an important role in schistosome transmission. We will first construct phylogenetic trees to indicate relationships among planorbid genera that will enable us to address the following questions:A. What genera of planorbid snails are the closest relatives of Biomphalaria and of other important genera of schistosome-transmitting hosts such as Bulinus or Indoplanorbis?
B. Did Biomphalaria evolve in the Neotropics?
C. Does shared susceptibility to infection with the same schistosome predict relatedness among genera of planorbid snails? We will also construct phylogenetic trees indicating relationships among the 31 extant species of Biomphalaria, and of Biomphalaria to other planorbid genera, to address the following questions:
D. Is Biomphalaria a monophyletic group?
E. How are the African and Neotropical representatives of Biomphalaria related to each other?
F. Is susceptibility to S. mansoni infection a primitive or derived trait among species of Biomphalaria and has susceptibility or resistance evolved more than once in the genus? and