A recent study compares the accumulation of mutations across many animal species and aims to explore the role of these genetic changes in ageing and cancer.

A team of scientists from the Wellcome Sanger Institute discovered that even though there is a huge variation in lifespan and size, different animal species’ natural lives end with similar numbers of genetic changes.

What genomes were analysed?

The researchers sequenced these species: black-and-white colobus monkey, cat, cow, dog, ferret, giraffe, harbour porpoise, horse, human, lion, mouse, naked mole-rat, rabbit, rat, ring-tailed lemur and tiger.

What are somatic mutations, and what do they do?

Human genes acquire around 20 to 50 genetic changes per year – called somatic mutations. While most of these mutations will be innocuous, some of them can start a cell on the path to cancer or diminish the normal functioning of the cell.

What were the findings of the study?

The longer the lifespan of a species, the slower the rate at which mutations occur. This is in line with the enduring theory that somatic mutations play a role in ageing.

The authors write “Giraffe and naked mole-rat, for instance, have similar somatic mutation rates (99 and 93 substitutions per year, respectively), in line with their similar lifespans (80th percentiles: 24 and 25 years, respectively), despite a difference of around 23,000-fold in adult body mass.”

The authors go on to say “Similarly, cows, giraffes and horses weigh much more than an average human, and yet have somatic mutation rates that are several fold higher, in line with expectation from their lifespan but not their body mass.”

What does body mass have to do with it? What is Peto’s Paradox?

The authors of the study note that “there appears to be no correlation between body mass and cancer risk across species. This observation, known as Peto’s paradox, suggests that the evolution of larger body sizes is likely to require the evolution of stronger cancer suppression mechanisms.

“Whether evolutionary reduction of cancer risk across species is partly achieved by a reduction of somatic mutation rates remains unknown.”

BMC Biology thus explains: “Peto’s Paradox is named after epidemiologist Richard Peto, who noted the relationship between time and cancer when he was studying how tumours form in mice. Peto observed that the probability of cancer progression was related to the duration of exposure to the carcinogen benzpyrene.

“He later added body mass to the equation, when he wondered why humans both contain 1000 times more cells and live 30 times longer than mice, yet the two species do not suffer incredibly different probabilities of developing cancer.

“Further, cancer was not a major cause of mortality for large and long-lived wild animals, despite the increased theoretical risks. How can this be?”

Dr Adrian Baez-Ortega, a first author of the study from the Wellcome Sanger Institute, says: “The fact that differences in somatic mutation rate seem to be explained by differences in lifespan, rather than body size, suggests that although adjusting the mutation rate sounds like an elegant way of controlling the incidence of cancer across species, evolution has not actually chosen this path.

“It is quite possible that every time a species evolves a larger size than its ancestors – as in giraffes, elephants and whales – evolution might come up with a different solution to this problem. We will need to study these species in greater detail to find out.”

Takeaways from the study

Dr Alex Cagan, the first author of the study from the Wellcome Sanger Institute, says: “To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising. But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate.

“This suggests that somatic mutations may play a role in ageing, although alternative explanations may be possible. Over the next few years, it will be fascinating to extend these studies into even more diverse species, such as insects or plants.”

The authors write that “Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. 

“These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.”