Researchers Examine Effect of Timing on Mutations

Timing may play a more important role in the survival of evolutionarily beneficial mutations in bacteria than previously thought, a discovery which might have implications on cancer research, according to a study by Harvard researchers released last month.

“For these sorts of dynamics, it’s easier to understand fundamentals in a flask, but this sort of evolution greatly affects people’s lives,” said Christopher J. Marx, associate professor of organismic and evolutionary biology.

Marx and his colleagues’ research began as an attempt to more fully understand how the bacterium Methylobacterium extorquens breaks down a toxic compound. In doing so, they inserted foreign plasmids, circular DNA molecules, into the bacteria. This was disadvantageous to the bacteria because they expended many resources when making the foreign proteins.

By manipulating various metabolic pathways in this way, Marx and his colleagues set out to analyze how the metabolic pathways were affected by these genetic changes.

However, the researchers encountered what Marx referred to as a “happy surprise.” They discovered that in many of the bacteria a transposon, which inserts itself into other genes, entered into the plasmid’s replication machinery, which decreased the bacterium’s production of the foreign proteins. This result was evolutionarily advantageous for the bacteria.

It also provided a way for the researchers to distinguish between all of the specific mutations which occurred.

“Because the mutations involved a jumping gene hopping into the plasmid, each time a mutation occurred, it occurred in a different place, a different junction between the plasmid and the host genome,” Marx said.

The movement allowed the researchers to observe that only some of the beneficial mutations were propagated in the population while other equally beneficial mutations were not.

Marx explained that the survival rate of various mutations depended on how well they could be integrated into the bacteria’s “complex dynamic of mutations” at a particular time. For instance, if a beneficial mutation had a role similar to that of another mutation, or was unable to “get along” with pre-existing mutations, it was less likely to propagate in the highly competitive environment.

Following the discovery, Marx and his colleagues are now trying to predict mutation survival rate with mathematical models.

Marx also described how these findings have implications for the study of infectious diseases that also have a complex and competitive environment for mutations. Marx noted cancer as a particular disease of interest because many types of tumors are environments in which a variety of beneficial mutations are attempting to propagate at a given time.