Cost-Efficiency Optimization Serves as a Conserved Mechanism that Promotes Osteosarcoma in Mammals.

Mutations that reduce the biosynthetic cost of ATP production or increase the gene translation efficiency (tAI) are favorable for rapid cell growth and proliferation and therefore likely to be observed in tumors. Whether the mutations in tumors optimize the trade-off between the ATP biosynthesis cost and gene translation efficiency by increasing the tAI/ATP ratio is currently unknown. We retrieved transcriptome data of normal and osteosarcoma tissue samples from humans and mice and identified tumor-specific mutations in each species by using stringent cutoffs and outgroup information. We compared the tAI/ATP values of genes before and after mutation. The tAI/ATP profile was found to be highly conserved in humans and mice, and also correlated with the essentiality of genes. Tumor-specific rather than shared mutations were found to lead to increased tAI/ATP values in both species. Thus, tumor-specific mutations were found to optimize the cost-efficiency trade-off by increasing the tAI/ATP ratio of genes in osteosarcoma. This may indicate an evolutionarily conserved mechanism that promotes tumorigenesis by facilitating rapid cell growth and proliferation.