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.
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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.