Cancer has left its 'footprint' on our evolution, according to a study which examined how the relics of ancient viruses are preserved in the genomes of 38 mammal species. The team found that as animals increased in size they 'edited out' potentially cancer-causing relics from their genomes so that mice have almost ten times as many ERVs as humans. The findings offer a clue as to why larger animals have a lower incidence of cancer than expected compared to smaller ones, and could help in the search for new anti-viral therapies.
Viral relics are evidence of the ancient battles our genes have fought against infection. Occasionally the retroviruses that infect an animal get incorporated into that animal's genome and sometimes these relics get passed down from generation to generation -- termed 'endogenous retroviruses' (ERVs). Because ERVs may be copied to other parts of the genome they contribute to the risk of cancer-causing mutations.
Now a team from Oxford University, Plymouth University, and the University of Glasgow has identified 27,711 ERVs preserved in the genomes of 38 mammal species, including humans, over the last 10 million years. The team found that as animals increased in size they 'edited out' these potentially cancer-causing relics from their genomes so that mice have almost ten times as many ERVs as humans. The findings offer a clue as to why larger animals have a lower incidence of cancer than expected compared to smaller ones, and could help in the search for new anti-viral therapies.
We set out to find as many of these viral relics as we could in everything from shrews and humans to elephants and dolphins,' said Dr Aris Katzourakis of Oxford University's Department of Zoology, lead author of the report. '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 (ERVs) -- and so be at greater risk of ERV-induced mutations -- but we've found this isn't the case. In fact larger animals have far fewer ERVs, so they must have found ways to remove them.'
A combination of mathematical modelling and genome research uncovered some striking differences between mammal genomes: mice (c.19 grams) have 3331 ERVs, humans (c.59 kilograms) have 348 ERVs, whilst dolphins (c.281 kilograms) have just 55 ERVs.
'This is the first time that anyone has shown that having a large number of ERVs in your genome must be harmful -- otherwise larger animals wouldn't have evolved ways of limiting their numbers,' said Dr Katzourakis. 'Logically we think this is linked to the increased risk of ERV-based cancer-causing mutations and how mammals have evolved to combat this risk. 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.'
Dr Robert Belshaw of Plymouth University Peninsula Schools of Medicine and Dentistry, School of Biomedical and Healthcare Sciences, added: "Cancer is caused by errors occurring in cells as they divide, so bigger animals -- with more cells -- ought to suffer more from cancer. Put simply, the blue whale should not exist. However, larger animals are not more prone to cancer than smaller ones: this is known as Peto's Paradox (named after Sir Richard Peto, the scientist credited with first spotting this). A team of scientists at Oxford, Plymouth and Glasgow Universities had been studying endogenous retroviruses, viruses like HIV but which have become part of their host's genome and which in other animals can cause cancer. Surprisingly, they found that bigger mammals have fewer of these viruses in their genome. This suggests that similar mechanism might be involved in fighting both cancer and the spread of these viruses, and that these are better in bigger animals (like humans) than smaller ones (like laboratory mice)."