![qbserve 1.82 qbserve 1.82](https://mac-cdn.softpedia.com/screenshots/Qbserve_7.jpg)
We show that the biological processes associated with cancer resistance vary across taxonomic groups (classes and orders of species), pointing to the diversity in the evolutionary paths and mechanisms for resisting cancer. We then use these cancer resistance–associated genes to build the first genomics-based predictor of cancer resistance for any species. To this end, we estimated the protein conservation scores across species including mammals, birds, and fish, identifying genes whose conservation levels are associated with cancer resistance estimated based on the species’ life span and body size. However, unlike previous studies that focused exclusively on mammals, here, we perform a comprehensive genome-wide comparative study aimed at identifying genes related to cancer resistance across a wide range of vertebrate species. We base our current study on a similar hypothesis, i.e., that resistance to cancer across species evolved by increased selection (either positive or negative) of certain genes with functional relevance to cancer. ( 19) identified regions with accelerated evolution in specific mammals, including several cancer-resistant species, which provided some insights on the cancer resistance mechanisms they have developed. ( 18) analyzed genes whose evolutionary rates across mammals correlate with body size and life span and discovered cancer resistance–related genes that are under increased evolutionary constraints in larger and longer-living mammals. Other studies focused on body size and longevity, yielding some insights into Peto’s paradox. Vazquez and Lynch ( 17) reported widespread tumor suppressor gene (TSG) duplications across both large and small Afrotherian species. ( 16) found that the number of paralogs of human cancer genes across mammals is positively correlated with the species’ life span but not body size.
![qbserve 1.82 qbserve 1.82](http://shooting-iron.ru/images/automat_1/kitay/QBS-06-3.jpg)
For example, Vicens and Posada ( 15) found that genes related to DNA repair and T cell proliferation have evolved under positive selection in mammals. Some have focused on known human cancer genes and their homologs. Numerous studies have adopted comparative genomics approaches to understand the evolution of cancer resistance mechanisms across mammals. It follows that different species must have evolved different cancer resistance mechanisms to fit their lifestyles, modifying the “baseline” probability of malignant transformation determined by body size, life span, and tissue stem cell division (see note S1 for a short review of such mechanisms). More drastically, the cancer-resistant bowhead whale ( 13) can weigh 100 metric tons, live for over 200 years ( 14), and have a million times more cells than mice. For example, humans do not have a higher cancer risk than mice despite having thousands of times more cells ( 10– 12). However, cancer risk does not correlate with body size across species, a contradiction known as Peto’s paradox ( 3, 8, 9). For humans, it has been shown that the risks of cancer development across different tissue types are correlated with their corresponding estimated number of lifetime stem cell divisions ( 5, 6) consistent with that, human cancer risk is correlated with body height ( 7). On the basis of this model, larger (and longer-living) animals are expected to have higher cancer incidence as they have more stem cell divisions overall, resulting in a higher likelihood of producing and propagating carcinogenic mutations. The multistage carcinogenesis model states that “individual cells become cancerous after accumulating a specific number of mutational hits” ( 3, 4).