From tumors to species: a SCANDAL hypothesis

Abstract

ᅟ: Some tumor cells can evolve into transmissible parasites. Notable examples include the Tasmanian devil facial tumor disease, the canine transmissible venereal tumor and transmissible cancers of mollusks. We present a hypothesis that such transmissible tumors existed in the past and that some modern animal taxa are descendants of these tumors. We expect potential candidates for SCANDALs (speciated by cancer development animals) to be simplified relatives of more complex metazoans and have genomic alterations typical for cancer progression (such as deletions of universal apoptosis genes). We considered several taxa of simplified animals for our hypothesis: dicyemida, orthonectida, myxosporea and trichoplax. Based on genomic analysis we conclude that Myxosporea appear to be the most suitable candidates for a tumor ancestry. They are simplified parasitic cnidarians that universally lack major genes implicated in cancer progression including all genes with Caspase and BCL2 domains as well as any p53 and apoptotic protease activating factor - 1 (Apaf-1) homologs, suggesting the disruption of main apoptotic pathways in their early evolutionary history. Further comparative genomics and single-cell transcriptomic studies may be helpful to test our hypothesis of speciation via a cancerous stage. REVIEWERS: This article was reviewed by Eugene Koonin, Mikhail Gelfand and Gregory M Woods.

Keywords: Cancer; Devil facial tumor disease; Evolution; Myxosporea; Myxozoa; Simplification; Speciation; Transmissible tumor.

Fig. 1

A comparison of SCANDAL candidates and control species in terms of PFAM domains. We used the PFAM list from a “census of human cancer genes” [22] and performed a PFAM search for the term “apoptosis”. We used 409 domains that were present in either of the two lists and present in 15 or more of the 29 control Metazoan species. The number of such domains absent in each species is shown on the y-axis. Parasitic species are marked by P