Why Smaller Mammals Are More Susceptible To Cancer

Mammalian genomes contain large numbers of endogenous retroviruses (ERVs), derived from multiple independent germline invasions over evolutionary time / University of Oxford
Janet Fang 19 Jul 2014, 03:04

Viruses leave their footprint in our evolution -- footprints that can alter our cancer risk. A new study examining viral relics in mammal DNA could explain why, compared to smaller animals, larger animals have a lower incidence of cancer than expected.

Retroviruses have been invading mammalian genomes for more than 100 million years, and sometimes they get incorporated into an infected animal’s genome and passed down from generation to generation. These long-lived traces are called endogenous retroviruses (ERVs).

A team led by Oxford’s Aris Katzourakis and Gkikas Magiorkinis identified 27,711 ERVs preserved in the genomes of 38 mammal species over the last 10 million years. With some mathematical modeling, the team found that larger mammals have fewer ERVs compared to smaller mammals, suggesting they must have found ways to remove them. The work was published in PLoS Pathogens this week. 

“We set out to find as many of these viral relics as we could in everything from shrews and humans to elephants and dolphins,” Katzourakis says in a news release. “Viral relics are preserved in every cell of an animal: Because larger animals have many more cells they should have more of these endogenous retroviruses -- and so be at greater risk of ERV-induced mutations -- but we've found this isn't the case.”

In fact, they found a negative correlation between animal body size and ERVs. For example, a 19-gram mouse has 3331 ERVs, a 59-kilogram person has 348 ERVs, and a 281-kilogram dolphin has just 55 ERVs.

This is the first study to show that a large number of ERVs in the genome is harmful. Simply put, animals wouldn’t have evolved ways to get rid of ERVs if they weren’t harmful. "We think this is linked to the increased risk of ERV-based cancer-causing mutations and how mammals have evolved to combat this risk," Katzourakis says. "So when we look at the pattern of ERV distribution across mammals it’s like looking at the ‘footprint’ cancer has left on our evolution."

ERVs that are immediately harmful typically wouldn’t get passed on, but they can, however, be copied to other parts of the genome. For example, they could jump into the middle of gene machinery that’s responsible for suppressing tumors, upping the risk of cancer-causing mutations.

Some cancers, such as leukemia, are directly linked to retroviruses. “But a lot of the time ERVs contribute to the number of things that need to go wrong in cells for cancers to arise,” Katzourakis explains. As animals get bigger, the number of cells increases, providing more opportunities for things to go awry. “So there is an evolutionary pressure for larger animals to reduce the number of ERVs,” he adds. 

Their study suggests that larger bodied animals control ERV replication in order to postpone cancer until a post-reproductive age. If we could identify the anti-viral resources of larger creatures, it could be possible to mimic these mechanisms to produce new anti-viral therapies.

Images: University of Oxford

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