The position of a gene on its chromosome influences its expression. Although this idea has been dawning on biologists for many years, confirmation has been elusive. A new study sheds some light on the way neighboring DNA alter how active a gene is and the extent to which it mutates.
An early view of genetics, still often taught at high school, holds that each gene single-handedly determines the protein that will be produced and therefore the biological consequences. Mutations in the gene’s DNA may alter the protein produced, and dominant versions may suppress the recessive ones, but the chromosomal environment was considered irrelevant.
As we’ve learned in recent years, things are far more complex. What was once termed “junk DNA” plays a big part in regulating genes' behavior. Moreover, the position of a gene within a chromosome, and the siting of genes around it, also make a difference. The details of how this works, however, have been unclear. Professor Călin Guet and PhD student Magdalena Steinrück of the Institute of Science and Technology, Austria, placed a gene for antibiotic resistance in four different positions within the Escherichia coli chromosome.
The gene gives E. coli the power to pump tetracycline, which would otherwise be deadly for the bacteria, out of the cell. In eLife, the authors report that, when exposed to low levels of antibiotic, tetA-yfp largely stayed switched off, irrespective of its location. However, as they raised tetracycline concentrations, mutations that turned the gene on allowed some bacteria to survive and multiply.
The capacity of the bacteria to meet the antibiotic threat depended greatly on the gene’s location, with some neighboring genes suppressing mutations that could have allowed the resistance gene to save the microbe’s life. A gene for fluorescence was inserted along with tetA-yfp, making the bacteria glow when tetA-yfp was expressed. This allowed the authors to visually confirm that the rate of tetA-yfp expression was the reason for some bacteria's survival.
"We show that genes can influence the mutation and adaptive potential of nearby genes," said Guet in a statement. "The organization of genes on a chromosome is both cause and consequence of evolutionary change."
Steinrück added: "It is similar to the way humans develop: People in your neighborhood can influence greatly how your future looks like.”
The discovery is important in the context of “jumping genes”, sections of DNA that can copy themselves and turn up in multiple places inside a genome. A gene that was only weakly expressed may be more potent in a new location. Genetic engineers may be able to create a map to identify where inserted genes will have the most potential.
It takes a genetic village to raise a protein.