If cells aren’t growing because they are under stress, how do new mutants appear?
The answer, according to researchers from Winship Cancer Institute at Emory University School of Medicine, is that a mutation appears in the RNA first. The mutation in the RNA results in a protein with augmented function that helps the cells grow, giving them a chance to replicate their DNA and for subsequent DNA mutations to exert their effects.
In a paper published in PLOS Genetics paper, researchers led by Paul Doetsch, PhD and colleague Bernard Weiss, MD, detail findings of a study that suggest that retromutagenesis occurred in E. coli bacteria forced to grow on the sugar lactose as their only source of energy.
The bacterial strain tested had a disabling mutation in a gene that, if functional, would allow the cells to use lactose, the researchers explained.
When exposed to high levels of nitrous acid, a DNA-damaging agent, mutations appeared in the bacteria and some of the bacteria could grow. By analyzing where exactly on the DNA the mutations occurred, the researchers concluded that retromutagenesis was contributing to bacterial growth.
The authors noted that retromutagenesis may explain previous observations of bacteria developing resistance to the antibiotic ciprofloxacin, as well as mutations in the human Ras oncogene, seen in many forms of cancer.
The research was supported by the National Institute of Environmental Health Sciences (P01-ES011163).