Comparative study of the evolution of cancer gene duplications across fish

Comparative studies of cancer-related genes not only provide novel information about their evolution and function but also an understanding of cancer as a driving force in biological systems and species' life histories. So far, these studies have focused on mammals. Here, we provide the first comparative study of cancer-related gene copy number variation in fish. Fishes are a paraphyletic group whose last common ancestor is also an ancestor of the tetrapods, and accordingly, their tumour suppression mechanisms should include most of the mammalian mechanisms and also reveal novel (but potentially phylogenetically older) previously undetected mechanisms. We have matched the sequenced genomes of 65 fish species from the Ensemble database with the cancer gene information from the COSMIC database. By calculating the number of gene copies across species using the Ensembl CAFE data (providing species trees for gene copy number counts), we used a less resource-demanding method for homolog identification. Our analysis demonstrates a masked relationship between cancer-related gene copy number variation (CNV) and maximum lifespan in fish species, suggesting that a higher number of copies of tumour suppressor genes lengthens and the number of copies of oncogenes shortens lifespan. Based on the positive correlation between the number of copies of tumour suppressors and oncogenes, we show which species have more tumour suppressors in relation to oncogenes. It could be suggested that these species have stronger genetic defences against oncogenic processes. Fish studies could be a largely unexplored treasure trove for understanding the evolution and ecology of cancer, providing novel insights into the study of cancer and tumour suppression, in addition to fish evolution, life-history trade-offs, and ecology.