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Safeguarding crucial genetic material

Cells have evolved a risk strategy prioritising which genes to guard most closely to prevent deleterious mutation, suggests new research.

 

Different genes mutate at different rates in the bacterium E. coli Credit: EMBL / I. Martincorena

 

Bacteria have evolved a mechanism to protect genes from random mutation, effectively reducing the risk of self-destruction say researchers at the European Molecular Biology Laboratory (EMBL). Their findings, published in Nature, answer a question that has been under debate for half a century and provide insight 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,” said Nicholas Luscombe, who led the research, “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.”

 

The team studied 120,000 tiny genetic mutations called single nucleotide polymorphisms (SNPs) in 34 strains of E. coli, and quantified how random the mutation rate was in different areas of the genomes. They found neutral mutation rates vary by more than an order of magnitude across 2,659 genes, and mutation hot and cold spots spanning several kilobases.

 

They also found key genes mutate at a much lower rate than the rest of the genetic material, which decreased the risk of such genes suffering a detrimental mutation.

 

“We were struck by how variable the mutation rate appears to be along the genome,” said Iñigo 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 disentangled the effects of mutation rate and natural selection on mutations, settling a long-stand debate in the field.

 

“For many years in evolution there has been as assumption that mutations occur randomly, and that selection ‘cleans them up’,” said Martincorena. “But what we see here suggests that genomes have developed mechanisms to avoid mutations in regions that are more valuable than others.”

 

The researchers believe similar mechanisms may be involved in the development of cancers, and now hope to investigate how this risk-managing gene protection works on a molecular level and what role it may play in tumour cells.