Large Body Size in Mammals is Accompanied by Duplication of Tumor Suppressor Genes

Larger mammals have many more cells than smaller mammals, and cancer risk increases with cell count, all other things being equal. Between species, body size does not correlate with cancer risk, however. Since species such as elephants and whales do not suffer an enormous rate of cancer in comparison to humans, clearly there are important differences in cellular biochemistry between these species. One example is that elephants have been found to have many copies of the tumor suppressor gene p53, and here researchers explore further to show that elephants have many copies of other tumor suppressor genes as well, each of which contributes to an overall lower risk of cancer despite a large body with many cells. Looking at other large mammals, this appears to be a fairly general mechanism accompanying increased size.

There is an incredible diversity of body sizes and lifespans among living mammals, remarkably even larger mammals lived in the recent past but are now extinct. In living mammals, an individual's body size and lifespan are among the greatest predictors for the likelihood of developing cancer, taller and older humans, for example, have a greater cancer risk than shorter and younger people. Between species, however, body size and lifespan are poor predictors of cancer risk, thus big and long lived species must have evolved ways to reduce their risk of developing cancer. By understanding how big, long-lived species evolved their enhanced tumor suppression mechanisms we can improve our understanding of genes involved in human cancer and inspire new cancer treatments.

We tracked how body size and the copy number of most protein coding genes changed in elephants and their smaller bodied relatives. We found that as large bodied elephants evolved from smaller bodied ancestors, their cancer risk decreased. While genes involved in tumor suppression were commonly duplicated in elephants and their relatives, elephants have a unique repertoire of tumor suppressor genes that evolved alongside their recent increase in body size. These data show that duplication of tumor suppressor genes facilitated the evolution of large body size by compensating for increasing cancer risk.

Link: https://doi.org/10.7554/eLife.65041

Comments

Seems like a good strategy for cell therapies and if we are able to print organs.

Posted by: Tom at February 10th, 2021 8:23 AM

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