The first study to compare the accumulation of mutations across many animal species has shed new light on decades-old questions about the role of these genetic changes in ageing and cancer. Researchers from the Wellcome Sanger Institute found that despite massive variations in lifespan and size, different animal species end their natural life with similar numbers of genetic changes.
The study, published in Nature, analyzed genomes from 16 species of mammal, from mice to giraffes. The authors confirmed that the longer the lifespan of a species, the slower the rate at which mutations occur, lending support to the long-standing theory that somatic mutations play a role in ageing.
Genetic changes, known as somatic mutations, occur in all cells throughout the life of an organism. This is a natural process, with cells acquiring around 20 to 50 conversions per year in humans. Most of these mutations will be harmless, but some of them can start a partition on the path to cancer or impair the cell's normal functioning.
Since the 1950s, some scientists have speculated that these mutations may play a role in ageing. But the difficulty of observing somatic mutations has made it challenging to study this possibility. In the last few years, technological advances have finally allowed genetic changes to be followed in normal tissues, raising hopes of answering this question1.
Another long-standing question is Peto’s paradox. Since cancers develop from single cells, species with larger bodies (and therefore more cells) should theoretically have a much higher cancer risk. Yet cancer incidence across animals is independent of body size. Animal species with large bodies are believed to have evolved superior mechanisms to prevent cancer. Whether one such mechanism reduces the accumulation of genetic changes in their tissues has remained untested.
In this study, researchers at the Wellcome Sanger Institute set out to test these theories by using new methods to measure somatic mutation in 16 mammalian species, covering a wide range of lifespans and body masses2. This included humans, mice, lions, giraffes, tigers, and the long-lived, highly cancer-resistant naked mole-rat, with samples provided by several organisations including the Zoological Society of London.
Whole-genome sequences were generated from 208 intestinal crypts3 taken from 48 individuals to measure mutation rates in single intestinal stem cells.
Analysis of the patterns of mutations (or mutational signatures) provided information on the processes at work. The researchers found that somatic mutations accumulated linearly over time and were caused by similar mechanisms across all species, including humans, despite their very different diets and life histories.
Evidence of a possible role of somatic mutations in ageing was provided by the researchers’ discovery that the rate of somatic mutation decreased as the lifespan of each species increased.
Source: Sanger Institute