Tumour suppressor genes fasta files for orthologous groups and hierarchical orthologous groups

Cetaceans are the longest-living species of mammals and the largest in the
history of the planet. They have developed mechanisms against diseases
such cancer, although the underlying molecular bases of these remain
unknown. The goal of this study was to investigate the role of natural
selection in the evolution of 1077 tumour suppressor genes (TSGs) in
cetaceans. We used a comparative genomic approach to analyse two sources
of molecular variation in the form of dN/dS rates and gene copy number
variation. We found a signal of positive selection in the ancestor of
cetaceans within the CXCR2 gene, an important regulator of DNA-damage,
tumour dissemination, and immune system. Further, in the ancestor of
baleen whales, we found six genes exhibiting positive selection relating
to such diseases as breast carcinoma, lung neoplasm (ADAMTS8) and
leukaemia (ANXA1). The TSGs turnover rate (gene gain and loss) was almost
2.4-fold higher in cetaceans as compared to other mammals, and noticeably
even faster in baleen whales. The molecular variants in TSGs found in
baleen whales, combined with the faster gene turnover rate, could have
favoured the evolution of their particular traits of anti-cancer
resistance, gigantism and longevity. Additionally, we report 71 genes with
duplications, of which 11 genes are linked to longevity (e.g. NOTCH3 and
SIK1) and are important regulators of senescence, cell proliferation and
metabolism. Overall, these results provide evolutionary evidence that
natural selection in tumour suppressor genes could act on species with
large body sizes and extended life span, providing novel insights into the
genetic basis of disease resistance.