The study, published online today in Nature, shows that bacteria have evolved a mechanism that protects important genes from random mutation, effectively reducing the risk of self-destruction. The findings answer a question that has been under debate for half a century and provide insights into how disease-causing mutations arise and pathogens evolve.
“We discovered that there must be a molecular mechanism that preferentially protects certain areas of the genome over others,” says Nicholas Luscombe, who led the research at EMBL-EBI. “If we can identify the proteins involved and uncover how this works, we will be even closer to understanding how mutations that lead to diseases like cancer can be prevented.”
Mutations are the reason each of us is unique. These changes to our genetic material are at the root of variation between individuals, and between cells within individuals. But they also have a darker side. If it affects an important gene – for example, rendering a tumour-suppressing gene useless – a mutation can have disastrous consequences. Nevertheless, protecting all genes from mutation would use up too many of the cell’s resources, just like holding all deposits in maximum-security safes would be prohibitively expensive. Iñigo Martincorena, a PhD student in Luscombe’s lab, has now found that cells evolved a ‘risk management’ strategy to address this issue.
Looking at 120 000 tiny genetic mutations called single nucleotide polymorphisms (SNPs) in 34 strains of the bacterium E. coli, the scientists were able to quantify how random the mutation rate was in different areas of the bacterial genomes. Their results showed that key genes mutate at a much lower rate than the rest of the genetic material, which decreases the risk of such genes suffering a detrimental mutation.
“We were struck by how variable the mutation rate appears to be along the genome,” says Martincorena. “Our observations suggest these bacteria have evolved a clever mechanism to control the rate of evolution in crucial areas of the genome.”
Using population genetics techniques, the researchers were able to disentangle the effects of mutation rate and natural selection on mutations, settling a long-standing debate in the field. Scientists have long thought that the chances of a mutation occurring were independent of its value to an organism. Once the mutation had occurred, it would undergo natural selection, spreading through the population or being eliminated depending on how beneficial or detrimental the genetic change proved to be.
“For many years in evolution there has been an assumption that mutations occur randomly, and that selection ‘cleans them up’,” explains Martincorena. “But what we see here suggests that genomes have developed mechanisms to avoid mutations in regions that are more valuable than others.”
Observations from studies of cancer genomes suggest that similar mechanisms may be involved in the development of cancers, so Luscombe and colleagues would now like to investigate exactly how this risk-managing gene protection works at a molecular level, and what role it may play in tumour cells.
Published online in Nature on 22 April 2012. DOI: 10.1038/nature10995.Policy regarding use
Sonia Furtado Neves | EMBL Research News
'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society
New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
20.02.2018 | Life Sciences
20.02.2018 | Medical Engineering
20.02.2018 | Physics and Astronomy