Intra-organismal evolution, cancer, and the challenges of an asexually reproducing immortal soma

Multicellularity is dependent on cellular cooperation and is susceptible to cheating cells. Once cheating cells evolve within a multicellular organism, the breakdown in cooperation can manifest as cancer. Most species are able to physically escape these progressively evolving cheating cells by undergoing a reproductive single cell bottleneck that frees the next generation from potential cancer. However, some species such as certain obligate asexual planarians, lack a single cell bottleneck and instead reproduce by fission. Such fission-based reproduction necessitates an immortal soma which may allow cheating cells to develop over evolutionary time. This suggests that immortal asexual planarians may have evolved extreme tumour suppressive mechanisms to deal with the challenges posed by cheating cell evolution. However, little is known about the tumour suppressive mechanisms of planarians, and there are no theoretical models exploring how this asexual mode of reproduction may impact selfish cell evolution within the body of immortal organisms. In this thesis, I will drive cancer in asexual planarians and allow them to evolve before analysing the cancers to isolate potential oncogenes and tumour suppressors. Additionally, I will test whether separate innovations of planarian asexuality consistently contain stem cells that evolve selfish behaviour and high intra-organismal competitiveness. Finally, I will build a theoretical framework for modelling how intra-organismal and inter-organismal competition interact to select for cell behaviour within immortal organisms. Taken together, this research has the potential to isolate genes allowing for extreme cancer resistance as well as explore the theoretical limitations of cell cooperation within immortal organisms.

BBSRC priority areas: "Healthy ageing across the lifecourse", "Lifelong Health and Wellbeing", "In vivo
techniques".