Adaptation génétique de la malaria à un nouvel environnement – MGANE

Despite remarkable advances in medical research during the 20th century, infectious diseases remain among the leading causes of death worldwide. The frequency of new pathogen emergence remains one of the main causes of this situation. Emerging diseases are those that have recently increased in incidence, have recently expanded their geographic distribution or their host range, or are caused by new pathogens. In other words, a key to disease emergence relies on the ability of a pathogen to adapt to new environmental conditions (drug treatments, new hosts, etc). Therefore, elucidating how pathogens adapt to new environments is a prerequisite to clearly understand how diseases emerge. One way to analyze how parasites adapt to new environmental conditions is to analyze past events of emergence. In this respect, Plasmodium falciparum, the agent of human malaria, constitutes an excellent model especially in South America. Firstly, we do know that the colonization of the new world occurred approximately 500 years ago. Secondly, during this colonization, P. falciparum faced drastic environmental changes defined by new human populations (Amerindians), new vector species, and, in more recent times, new drugs. Thirdly, the genome of the parasite has been entirely sequenced and overall-genome single nucleotide polymorphisms (SNPs) have been defined, offering a unique opportunity to study adaptation at a genome-wide scale. The main objective of our project is to analyze the polymorphism of the entire genome of P. falciparum in several populations in South America (French Guiana) and Africa to determine which genes (or genomic regions) have been involved in the adaptation to the environmental changes that have scattered its emergence in the New World (new vector species, new human populations, drug treatment). We will search for the genes that display the signature of recent positive-selection events, after having controlled for demographical changes. To determine these candidate genomic regions, we will use a newly characterized large bank of dense single nucleotide polymorphisms (SNPs) distributed throughout the genome of P. falciparum, the statistical tools of population genetics, and an appropriate sampling strategy of parasite populations living in different conditions. A first step in the study will be to take into account the demographic changes of parasite populations within African and American samples. Our sampling strategy is designed for multiple comparisons in the patterns of selection experienced by P. falciparum (e.g., between the newly founded parasite populations in South America and their potential African sources; within the Americas, between Amerindian and Maroon (direct descendants of slaves) hosts; and between the African human populations that live either in African or in American environments, i.e., French Guiana). Altogether, this will allow us to identify the genes involved in the adaptation to new human populations, to new vector species, and, more recently, to new antimalarial drugs. The genome-wide scan for positive selection will identify candidate genes that may have been involved in any of three adaptations, namely (i) the adaptation to a new vector species, (ii) the adaptation to new human populations (Amerindian), and (iii) the adaptation to the antimalarial drugs used there. Our project will also compare the evolution of these different genomic regions in populations living in different environments. Our project will thus reveal the fundamental mechanisms of the evolution of a re-emerging parasite in response to new hosts and chemical environments, which are essential to deepen our capacity to evaluate, even predict, how parasites may respond to particular modifications in its environment such as the development of a vaccine targeting particular antigens or the introduction of new drugs. Understanding how a parasite adapts to a new host species is also very important in the context of new emerging infectious diseases.