Genômica comparativa de Schistosoma mansoni: biodiversidade molecular à luz da evolução

Abstract

Schistosoma mansoni is one of the three main causative agents of human schistosomiasis, a disease with high prevalence and morbidity, causing a vast socio-economic impact. Schistosomiasis is endemic in 78 countries where 243 million people require preventive chemotherapy and other 779 million live in areas of risk of infection. The S. mansoni genome was completely sequenced and the predicted proteome contains over 11.000 proteins. However, more than 45% remain without a predicted function or experimental characterization. The availability of genomic information allows the acceleration of S. mansoni Systems Biology knowledge as well as the evolutionary relationships with hosts, resulting in improved understanding about schistosomiasis and hopefully the creation of new disease control methods. This thesis is focused on the application of the comparative analyses to address the complexity of biological functions at a systems level through the reconstruction of the evolutionary history of macromolecules encoded by S. mansoni genome. Furthermore, additional efforts were made in order to improve the functional annotation of S. mansoni proteome based on the identification of homologues with known function in other organisms. In summary, the four chapters that structure this thesis contribute to solving persisting scientific challenges that aim at understanding of: Which genes were gained, lost or duplicated in the S. mansoni genome? Which were the evolutionary processes that shaped this parasite's molecular biodiversity? How host-parasite co-evolution allowed this helminth to survive for years in human bloodstream, a potentially hostile environment, protected against host immune system or actively reacting making host immune response ineffective? What are potential new therapeutic targets to alternative drugs and vaccine development? Using a multidisciplinary and integrative approach, we improved the functional annotation of S. mansoni predicted proteome, contributed to the knowledge of evolutionary relationships of this parasite in comparison to other eukaryotes, identified expanded protein families that are related to parasite biology and highlighted potential therapeutic targets that can be used against schistosomiasis. Continuing this work, comparative analyses involving genomic, transcriptomic, and proteomic data from other helminth parasites and vectors as well as experimental characterization of promising targets will supply more information regarding parasite biology towards prevention of disease progression.