Evolutionary diversity of oncogenes and the implications for cancer vulnerability in large-brained mammals
Description
Comparative studies in humans and domestic species have revealed that meningiomas and gliomas are dominant brain tumor profiles and likely occur in similar frequencies in other mammals. However, determining the incidence rate in non-domestic mammals is hampered by several sampling and diagnostic challenges. Here we compared oncogene variation with respect to brain and body size in other large-brained mammals (Euungulata, Carnivora and Cetaceans) with the aim of gaining unique insight into its potential impact on cancer susceptibility. The Entrez system was used to obtain mRNA sequences (IDH1, TP53, and HERC2) and multiple sequence alignment, phylogenetic reconstruction, and BLAST searches were preformed to identify conserved and lineage-specific variants. Hamming distances were correlated with species body and brain size data and analyzed using regression and principal component analysis. Our results revealed for IDH1, a MYB-related sequence was conserved in Carnivora, mutated in Cetaceans and Perissodactyla, and absent in Artiodactyla. Genetic distances correlated positively with body and brain size. TP53 contained a Carnivora-specific viral-like fragment, with variation more strongly associated with brain size. HERC2 exhibited unique variants in Carnivora and Perissodactyla, with brain mass as the strongest predictor. BLAST searches linked the IDH1 variant to MYB dysregulation, suggesting increased cancer susceptibility in Cetaceans and Perissodactyla and alternate pathways in Artiodactyla. Variants in TP53 and HERC2 showed homology to dsDNA tailed bacteriophages, possibly reflecting ancient horizontal gene transfer events. In conclusion, These findings suggest that oncogene diversity scales with body and brain size and likely reflect evolutionary pressures influencing cancer susceptibility in large-brained mammals.
Citation Information
Harris, Zachary and Spocter, Muhammad A., "Evolutionary diversity of oncogenes and the implications for cancer vulnerability in large-brained mammals" (2026). Office of Research DMU Research Symposium. 108.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/108
Evolutionary diversity of oncogenes and the implications for cancer vulnerability in large-brained mammals
Comparative studies in humans and domestic species have revealed that meningiomas and gliomas are dominant brain tumor profiles and likely occur in similar frequencies in other mammals. However, determining the incidence rate in non-domestic mammals is hampered by several sampling and diagnostic challenges. Here we compared oncogene variation with respect to brain and body size in other large-brained mammals (Euungulata, Carnivora and Cetaceans) with the aim of gaining unique insight into its potential impact on cancer susceptibility. The Entrez system was used to obtain mRNA sequences (IDH1, TP53, and HERC2) and multiple sequence alignment, phylogenetic reconstruction, and BLAST searches were preformed to identify conserved and lineage-specific variants. Hamming distances were correlated with species body and brain size data and analyzed using regression and principal component analysis. Our results revealed for IDH1, a MYB-related sequence was conserved in Carnivora, mutated in Cetaceans and Perissodactyla, and absent in Artiodactyla. Genetic distances correlated positively with body and brain size. TP53 contained a Carnivora-specific viral-like fragment, with variation more strongly associated with brain size. HERC2 exhibited unique variants in Carnivora and Perissodactyla, with brain mass as the strongest predictor. BLAST searches linked the IDH1 variant to MYB dysregulation, suggesting increased cancer susceptibility in Cetaceans and Perissodactyla and alternate pathways in Artiodactyla. Variants in TP53 and HERC2 showed homology to dsDNA tailed bacteriophages, possibly reflecting ancient horizontal gene transfer events. In conclusion, These findings suggest that oncogene diversity scales with body and brain size and likely reflect evolutionary pressures influencing cancer susceptibility in large-brained mammals.
