Phage viruses, used to treat antibiotic resistance, gain an advantage by blocking the ability of their competitors to reproduce

Historically, curious bits of DNA hidden in the genomes of all kingdoms of life have been ignored because they don’t seem to have a role to play in the competition for survival, or so researchers thought.

These DNA fragments were called “selfish genetic elements” because they exist, scientists believe, simply to reproduce and propagate, without any benefit to their host organisms. They were considered genetic hitchhikers that were passed down without consequence from one generation to the next.

Research by scientists at the University of California, San Diego, has provided new evidence that these DNA elements may not be so selfish after all. Instead, they now appear to play a significant role in the dynamics between competing organisms.

Publication in the journal ScienceResearchers from the School of Biological Sciences studied the selfish genetic elements of bacteriophages (phages), viruses considered the most abundant organisms on Earth. To their surprise, the researchers discovered that the selfish genetic elements known as “mobile introns” give their viral hosts a clear advantage when competing with other viruses: the phages have weaponized the mobile introns to disrupt the ability of competing phage viruses to replicate.

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

Decades ago, biologists had already noticed the existence of selfish genetic elements, but had not been able to characterize the role they played in helping the host organism survive and reproduce. In the new study, which focused on the study of “giant” phages, the researchers analyzed the dynamics of two phages co-infecting a single bacterial cell and competing against each other.

The researchers took a close look at endonuclease, an enzyme that cuts DNA. The studies showed that the endonuclease in a phage’s mobile intron interferes with the genome of the competing phage. As a result, the endonuclease is now considered a combat tool since it has been shown to cut a critical gene in the genome of the competing phage. This sabotages the competitor’s ability to properly assemble its own offspring and reproduce.

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

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

“We were able to clearly define the mechanism that confers an advantage and how it happens at the molecular level,” said Chase Morgan, a graduate student in biological sciences and co-first author of the study. “This incompatibility between selfish genetic elements becomes a molecular war.”

The results of this study are important because phage viruses are emerging as therapeutic tools in the fight against antibiotic-resistant bacteria. As doctors use “cocktails” of phages to fight infections in this growing crisis, this new information is likely to come into play when multiple phages are used. Knowing that some phages use selfish genetic elements as weapons against other phages could help researchers understand why some phage combinations fail to achieve their full therapeutic potential.

“The phages studied can be used to treat patients with bacterial infections associated with cystic fibrosis,” said Joe Pogliano, professor of biological sciences. “Understanding how they compete with each other will allow us to create 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.