When Cancer Becomes a SCANDAL

Jabale Rahmat
Junior
School of Life Sciences
Independent University, Bangladesh

March 23rd, 2019

Have you ever heard of a bacterium afflicted by cancer? Of course not. Cancer is an accidental consequence of multicellularity. Multicellular organisms, like animals, have tightly regulated numbers and distributions of many different types of cells that cooperate as a functional whole. Cancer occurs when some of these cells decide to go rebel and keep dividing even at the expense of the organism. We could think of cancers as cellular parasites.

Actual parasites are transmitted from host to host, but we obviously do not see cancers being transmitted between humans. There are, however, transmissible cancers that have been discovered in other animals, leading to some fascinating speculation on what actually distinguishes these cancers from parasites.

Metzger et al, in their 2016 paper [1], reported that mussels, cockles, and golden carpet shell clams are afflicted by independent lineages of leukemia-like transmissible cancers, adding to three other kinds of transmissible cancers that had been previously known (in dogs, Tasmanian devils, and soft-shell clams, respectively). In these bivalve species, cancerous hemocytes (the equivalent of blood cells in invertebrates) get transmitted between individuals of the same species through the water as they breathe by filtering oxygen directly from the water. In all three cases, while cancer may be occurring spontaneously with some frequency, the transmissible forms appear to be responsible for most of the cases in natural populations. Interestingly, they discovered that the golden carpet shell clams got their cancer from another clam species, the pullet carpet shell clams, suggesting a cross-transmissible event of cancer. But the pullet carpet shell clams are resistant to the cancer. This suggests that they may have evolved resistance to this transmissible cancer, owing to strong selection pressures exerted by the cancer. Adaptation like this would mirror the dynamics of host-pathogen coevolution.

A healthy Tasmanian devil. University of Tasmania

While it is difficult to know whether this was indeed an adaptation,  Epstein et al. [2] were able to ask a similar question about a transmissible cancer in Tasmanian devils in a 2016 study. The devil facial tumor disease (DFTD), the transmissible cancer found in Tasmanian devils, had been discovered in the Tasmanian island of Australia in 1996. The disease, which is lethal in virtually all cases, has since been devastating Tasmanian devil populations. The cancer is able to spread between individuals by evading and suppressing immune responses. But against all odds, the Tasmanian devils have successfully avoided extinction and managed to persist. Epstein and colleagues, in the 2016 study, investigated whether the Tasmanian devils had evolved resistance to DFTD. Using tissue samples from Tasmanian devils that were collected before and after DFTD ravaged the populations, they were able to show different populations of Tasmanian devils had undergone rapid evolution in regions of the genome containing genes related to immune function and cancer risk. This suggests that strong selection pressure imposed by the DFTD has resulted in evolution of improved defenses against the cancer in Tasmanian devils. An arms race could ensue, leading to the evolution of DFTD to avoid these new defenses.

If these transmissible cancers are genetically distinct and act essentially like parasites, why do we not think of them as distinct species? Could they perhaps represent the origin of new species? Recently, Panchin et al. proposed the SCANDAL (Speciated by CANcer Development Animal) hypothesis, which posits that speciation may sometimes arise from transmissible cancers [3].

By using bioinformatic approaches, they showed that one form of obligate parasites of fish called Myxosporea may have arisen in this manner. They provide evidence that its ancestor was a free-living cnidarian that had lost a large number of genes involved in apoptosis and tumor-suppression. They hypothesized that this loss of genes may have taken in a single somatic cell, leading to cancer, which was followed by the spread of the cancer cells to fish. This may have ultimately led to the parasitic relationship we observe today. While an attractive hypothesis, the loss of these genes may also have occurred as part of an overall simplification of the genome of the free-living cnidarian as it adapted to a parasitic lifestyle, much like how obligate intracellular bacteria tend to have reduced genome sizes.

Mechanisms of speciation remain mired in mysteries, but we can at least state with some certainty that there have been several different mechanisms at work in the evolutionary history of life on earth. Whether or not the SCANDAL hypothesis finds more support, the Tasmanian devil study points to an essential truth. If it spreads like a parasite, and if it drives adaptation like a parasite, it may as well be one.

Bibliography:

1. Metzger MJ, Villalba A, Carballal MJ, et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature. 2016;534(7609):705-709. doi:10.1038/nature18599

2. Epstein B, Jones M, Hamede R, et al. Rapid evolutionary response to a transmissible cancer in Tasmanian devils. 2016. doi:10.1038/ncomms12684

3. Panchin AY, Aleoshin V V, Panchin Y V. From tumors to species : a SCANDAL hypothesis. 2019:1-10.

Jabale is a Junior in the School of Life Sciences at IUB majoring in Biochemistry. He is a future scientist who is crazy about everything related to biology, especially genetics.