Abstract
Transmissible cancers are malignant cell lineages that have evolved the ability to colonize new individuals by transmission of cancer cells themselves. Previously considered rare exceptions in vertebrates, with only one lineage described in dogs and two in Tasmanian devils, the findings since 2015 of five lineages in several species of marine bivalves have questioned their rareness in this group. These new parasitic forms, which are unique biological entities not quite like anything else, raise many questions. In bivalves, except the descriptions of the different lineages, few data were available on their biology, ecology and evolution. My thesis focuses on the study of transmissible cancers in Mytilus sp. mussels. By combining several approaches of ecology, evolutionary biology and functional biology, my work allowed to describe the distribution and prevalence of this cancer in European mussel populations, to study the evolutionary history of these transmissible cancer lineages, as well as to study the host responses to invasion by cancer cells. We showed that (1) populations of the two European mussels M. edulis and M. galloprovincialis are affected by a single transmissible cancer lineage (MtrBTN2) that initially emerged in a M. trossulus host, also found in M. chilensis in Chile and in M. trossulus in the Sea of Japan, which is different from the first lineage initially described in the M. trossulus populations of British Columbia (MtrBTN1), (2) the prevalence is globally low but varies among host genetic backgrounds and habitats, (3) maritime traffic seems to create epidemiological gateways between ports explaining a higher prevalence in these anthropized habitats, (4) despite clonal evolution MtrBTN2 is polymorphic which suggests a complex and possibly ancient evolutionary history that led to the evolution of at least two sub-lineages in Europe, (5) the dynamics of intra-host invasion by the cancer seem to depend on the recipient and the donor individual in the context of experimental infections and (6) this invasion seems to induce in the recipient individuals a predominantly humoral immune response and a tissue remodeling associated with a prolonged inflammatory response. These different results allow a better understanding of the dynamics of this very particular host-cancer system and open many perspectives. More than being unique and intriguing biological entities that allow us to study cancer from an original evolutionary viewpoint, transmissible cancers are ideal biological models for many fundamental questions in biology.