How bacteria protect key genes from mutation and implications for cancer

03 May 2012

Scientists have discovered that bacteria have evolved a way to safeguard their most important genes against random mutations. The work provides insights into how disease-causing mutations arise in humans, such as those that occur in cancer.

The study of 34 bacterial genomes answers a question that has been under debate for half a century.

In the bacterium E. coli, different genes mutate at different rates

In the bacterium E. coli, different genes mutate at different rates, following a risk management strategy like those used in the stock market.
© Iñigo Martincorena







Genetic mutations are responsible for variation between individuals in a population, and between cells within individuals. It has long been thought that mutations occur randomly, but that whether a mutation will become fixed in the population depends on selection - where individuals with advantageous mutations tend to reproduce more successfully.

Using population genetics techniques, the researchers disentangled the effects of mutation rate and selection on changes in the bacterial genomes. They showed that, much like a bank choosing which safe deposit boxes will get the highest possible security, bacteria use a 'risk management' strategy to prioritise which genes will get preferential treatment.

The team looked at 120,000 tiny genetic mutations called single nucleotide polymorphisms (SNPs) in 34 strains of E. Coli. By quantifying how random the mutation rate was in different areas of the genomes, they showed that key genes mutate at a much lower rate.

The work was carried out by Nick Luscombe of the London Research Institute (now part of the Francis Crick Institute) with colleagues from the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) in the UK, the Okinawa Institute of Science and Technology in Japan, and the National Centre for Biological Sciences in India.

Dr Luscombe said: "We were struck by how variable the mutation rate is along the genome. We have demonstrated that these bacteria have evolved a clever mechanism to control the rate of evolution in crucial areas of the genome. This is important for many areas of health research. For example, similar mechanisms may occur in the development of cancers."

"For many years in evolution there has been an assumption that mutations occur randomly, and that selection 'cleans them up'," explained Inigo Martincorena of EMBL-EBI. "But what we see here is that genomes have developed mechanisms to avoid mutations in regions that are more valuable than others."

Further research is now needed to find out exactly how, at a molecular level, this happens. Dr Luscombe added: "There must be a molecular mechanism that preferentially protects certain areas of the genome over others. If we can identify the proteins involved and uncover how this works, we will be much closer to understanding how disease-causing mutations arise in other organisms."

The paper, 'Evidence of non-random mutation rates suggests an evolutionary risk management strategy', was published recently in Nature.

  • Bacteria have evolved a way to protect their crucial genes against random mutation
  • The scientists studied 34 bacterial genomes and found that the rate of random mutations was much lower in the most important genes
  • The results have implications for human health research - similar mechanisms are thought to occur in the development of cancers