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.
Viral relics are proof of the ancient battles our genes have fought against infection. Occasionally the retroviruses that infect a pet get integrated into that animal’s genome and sometimes these relics get passed down from one generation to another C termed ‘endogenous retroviruses’ (ERVs). Because ERVs may be copied to other areas of the genome they contribute to the chance of cancer-causing mutations.
Now a team from Oxford University, Plymouth University, and the University of Glasgow has identified 27,711 ERVs preserved within the genomes of 38 mammal species, including humans, over the last Ten million years. They found that as animals increased in dimensions they ‘edited out’ these potentially cancer-causing relics using their genomes to ensure that mice have almost 10 times as numerous ERVs as humans. The findings provide a clue 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.
A report from the scientific studies are published within the journal PLOS Pathogens.
“We set out to find as numerous of these viral relics once we could in from shrews and humans to elephants and dolphins,” said Dr Aris Katzourakis of Oxford University’s Department of Zoology, lead author from the report. “Viral relics are preserved in each and every cell of an animal: Because larger animals have many more cells they should convey more of these endogenous retroviruses (ERVs) C and so attend and the higher chances of ERV-induced mutations C but we’ve found this is not 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 actually the first time that anyone indicates that using a large number of ERVs inside your genome should be harmful C otherwise larger animals wouldn’t have evolved ways of limiting their numbers,” said Dr Katzourakis. “Logically we believe this really is from the increased chance of ERV-based cancer-causing mutations and how mammals have evolved to combat this risk. Then when we glance in the pattern of ERV distribution across mammals it’s like exploring 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 brought on by errors occurring in cells as they divide, so bigger animals with more cells ought to suffer more from cancer. Put simply, nowhere whale should not exist. However, larger animals aren’t more prone to cancer than smaller ones: this is whats called Peto’s Paradox (named after Sir Richard Peto, the scientist credited with first spotting this). A group 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 discovered that bigger mammals have fewer of those viruses within their genome. This suggests that similar mechanism may be involved with fighting both cancer and the spread of these viruses, which these are better in bigger animals (like humans) than smaller ones (like laboratory mice).”
ERVs that are immediately harmful to a pet tend not be handed down, are they all troublesome is the fact that having arrived at one location in a genome the replication process means they may be copied across, ‘jumping’, to somewhere else. ERVs can, for instance, ‘jump’ in to the middle of gene machinery accountable for suppressing tumors, damaging it and ratcheting in the chance of mutations turning into cancer.
“We all know that some cancers, such as t-cell leukaemia, are directly associated with retroviruses but a lot of the time ERVs contribute to the number of stuff that need to go wrong in cells for cancers to arise,” said Dr Katzourakis. “As animals develop so the quantity of cells increases and there tend to be more opportunities for items to fail, so there is definitely an evolutionary pressure for larger animals to reduce the amount of ERVs.”
Dr Gkikas Magiorkinis of Oxford University’s Department of Zoology, a writer from the report, said: “We know that taller individuals have greater risk for some cancers, which fits our study about ERVs posing evolutionary pressure through cancer. Yet we still have no evidence that ERVs might have causal links with cancer in humans, while they clearly cause cancers in other animals for example mice. We have to search inside a more systematic method to see if ERVs cause cancer in humans, and our study suggests that viral pathogenic mechanisms in larger animals like humans could be more complicated than those observed in smaller animals.”
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 because they divide, so bigger animals with more cells ought to suffer more from cancer. Put simply, nowhere whale should not exist. However, larger animals are not 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 have 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 may be involved with fighting both cancer and the spread of those viruses, and that these are better in bigger animals (like humans) than smaller ones (like laboratory mice).”
The study shows that larger creatures must have more effective anti-viral genes and resources than smaller ones and, if these can be identified, in the future it may be possible to mimic these mechanisms to produce new anti-viral therapies.
The new study is relevant to Peto’s Paradox, an observation produced by Sir Richard Peto the incidence of cancer does not appear to correlate with the number of cells in an organism. “Our work doesn’t solve Peto’s paradox as a whole but is has solved it according of infection,” said Dr Katzourakis.