Phage viruses, used to treat antibiotic resistance, gain an advantage by limiting the reproductive capacity of competitors

Curious bits of DNA tucked inside genomes across all kingdoms of life have historically been overlooked because they don’t seem to play a role in the competition for survival, or so scientists thought.

These pieces of DNA have become known as “selfish genetic elements” because they exist, as far as scientists can tell, simply to reproduce and multiply without any benefit to the host organisms. They were considered genetic trackers that were passed down from generation to generation for no reason.

Research conducted by researchers at the University of California, San Diego has provided fresh evidence that such elements of DNA may not be so selfish after all. Instead, they now appear to greatly influence the dynamics between competing organisms.

Publishing in a journal Science, researchers from the School of Biological Sciences studied selfish genetic elements in bacteriophages (phages), viruses that are thought to be the most abundant organisms on Earth. To their surprise, the researchers discovered that selfish genetic elements known as “mobile introns” gave their viral hosts a distinct advantage in competition with other viruses: Phages weaponized the mobile introns to disrupt the reproductive ability of rival phage viruses.

“This is the first time that a selfish genetic element has been shown to provide a competitive advantage to the host organism it invades,” said study co-author Erica Birkholz, a postdoctoral fellow in the Department of Molecular Biology. “Understanding that selfish genetic elements are not always purely ‘selfish’ has broad implications for better understanding the evolution of genomes in all kingdoms of life.”

Decades ago, biologists noted the existence of selfish genetic elements, but were unable to characterize any role they play in helping the host survive and reproduce. In the new study, which focused on investigating “jumbo” phages, the researchers analyzed the dynamics when two phages co-infected a single bacterial cell and competed against each other.

They looked closely at endonuclease, an enzyme that serves as a tool for cutting DNA. Studies have shown that an endonuclease from a mobile intron of one phage interferes with the genome of a competing phage. Therefore, the endonuclease is now considered a combat tool because it has been documented to cleave an essential gene in the genome of a competing phage. This sabotages the competitor’s ability to appropriately assemble its own offspring and reproduce.

“This weaponized intron endonuclease provides a competitive advantage to the phage that carries it,” Birkholz said.

The researchers say this finding is particularly important in the evolutionary arms race between viruses because of the constant competition in co-infection.

“We were able to clearly delineate the mechanism that provides the benefit and how it happens at the molecular level,” said Biological Sciences graduate student Chase Morgan, co-author of the paper. “This incompatibility between selfish genetic elements becomes molecular warfare.”

The results of the study are important because phage viruses are emerging as therapeutic tools in the fight against antibiotic-resistant bacteria. As doctors deploy phage “cocktails” to fight infections in this growing crisis, new information will likely come into play as more phages are implemented. Knowing that some phages use selfish genetic elements as weapons against other phages could help researchers understand why certain combinations of phages may not reach their full therapeutic potential.

“The phages in this study can be used to treat patients with bacterial infections associated with cystic fibrosis,” said Professor of Biological Sciences Joe Pogliano. “Understanding how they compete with each other will allow us to make better cocktails for phage therapy.”

The authors of the article are: Erica Birkholz, Chase Morgan, Thomas Laughlin, Rebecca Lau, Amy Prichard, Sahana Rangarajan, Gabrielle Meza, Jina Lee, Emily Armbruster, Sergey Suslov, Kit Pogliano, Justin Meyer, Elizabeth Villa, Kevin Corbett, and Joe Pogliano.