Blue whales exhibit a resistance to cancer despite their size and lifespan, and as numerous studies have found that when the size of organisms increases, the probability of acquiring tumors decreases. This trend happens due to enhanced DNA repair mechanisms. The research ran a comparative genomic analysis on key genes responsible for the reparation of genetic material in the process of BER. Using NIH databases and benchling, sequences of UNG DNA glycosylase, PNKP, APEX1, DNA polymerases, Lig III, PARP1 and XRCC1, the proteins were aligned and compared to human counterparts to identify amino acid substitutions and assess the functional impact on the proteins. Results were able to showcase that proteins exhibit a substantial difference from those present in humans and blue whales, with pairwise identities of as 64.00% in PNKP and 97.92% DNA glycosylase, blue whale proteins which have a lower pairwise identity; For example PNKP reaching an instability index of 50.65% compared to 35.34% in humans. While proteins with similar pairwise identities showcased a higher stable form of the protein. For example, the blue whale’s UNG presents an instability index of 47.16% compared to 47.19% in humans. Although the isoforms of many of these genes present in blue whales present a higher instability, a high turnover reaction rate serves as a solution to this instability. Results suggest that blue whales have evolved to have an optimized BER pathway though protein-protein interactions. This work helps to pinpoint specific protein candidates for future wet lab studies aimed at reinforcing human DNA reparation mechanisms.
Keywords
Cancer, Genomic analysis, Cetaceans, Tumor suppressor genes.