- Adapting to the host immune system: As transmission increased, the tumor faced greater host immune selection. This is expected from theory to favor alleles that reduce antigen presentation and immune recognition, and tumor variants with such loss-of-function mutations increased in frequency with geographic spread.

- Adapting to the transmission route: As transmission increased and became density dependent, transmission bottlenecks became larger and more frequent, increasing the importance of rapid growth for successful transmission. This theory predicts rapid growth should evolve under these circumstances, and tumor latency became shorter as it spread across Tasmania.

- Acquiring new transmission routes: The tumor initially required direct contact for transmission, resulting from tissue biting. As the tumor invaded new geographic regions, it encountered novel host genotypes that likely differed in immune function and biting behaviors. This theory predicts increased transmission routes under these circumstances, and a second transmissible tumor variant evolved that can spread via aerosolized tumor cells that transmit through the respiratory system.