Mechanisms and evolutionary significance of hyperploidy variations in a long-lived parasitic cancer

Transmissible cancers are fascinating recently discovered biological entities.

They have acquired the ability to cross host boundaries and spread between animals, even sometimes interspecifically, by the direct transfer of cancerous cells.

In addition, despite asexual reproduction they have been shown to persist for hundreds or thousands of years in host populations.

Importantly, in the absence of known sexual-like reproduction mechanism, transmissible cancers must cope with clonal degeneration.

One challenging question that arises is to understand the evolutionary processes and molecular mechanisms by which genetic diversity can maintain in such a long-term clonal context. Several transmissible cancer lineages have been described in Bivalvia and they have all in common hyperploidy.

Some distinct sub-lineages (with a common founder host) coexist in host populations with specific degrees of hyperploidy (2 to 10 times the host cell DNA content).

Hence, the hypothesis that hyperploidization concurs to the persistence and long-term evolution of these transmissible cancers must be considered.

HYPERCAN aims to decipher the evolutionary significance of hyperploidy and of its variation to amplify clonal heterogeneity in mussel transmissible cancers (MtrBTN).

We will use a multi-disciplinary approach combining phenotyping and “multi-omics” in order to test evolutionary hypotheses. We will answer 3 main questions:1. Ploidy and fitness. Does a correlation exist between ploidy degrees and fitness?2.Evolutionary dynamics. How does evolution proceed in MtrBTN cancers?3.Hyperploidization mechanisms.

How is hyperploidy generated and what is the fate of newly evolved hyperploid lineages?The project will have multiple outputs and applications among which to understand the genetic mechanisms driving the evolution of long-living cancers and to provide useful elements for the assessment of evolutionary and phenotypic effects associated with hyperploidization in cancers.