The degree to which selfish genetic elements are actually selfish may need a rethink. For decades, it has been assumed that the typical selfish genetic element is a bit of DNA that resides in a host’s genome and propagates itself through a population of hosts—no matter whether it lends the hosts that carry it a survival advantage or not. Little wonder that selfish genetic elements also came to be called parasitic DNA.
But now it appears that selfish genetic elements might not be so selfish after all. According to new research conducted by scientists at the University of California, San Diego, a certain kind of selfish genetic element—an intron containing a homing endonuclease—can give its host, a phage, a survival advantage over the phage’s peers.
Detailed findings recently appeared in Science, in an article titled, “An intron endonuclease facilitates interference competition between coinfecting viruses.”
“[We] studied intron-encoded homing endonuclease gp210 in bacteriophage ΦPA3 and found that it contributes to viral competition by interfering with the replication of a coinfecting phage, ΦKZ,” the article’s authors wrote. “We show that gp210 targets a specific sequence in ΦKZ, which prevents the assembly of progeny viruses.
“This is the first time a selfish genetic element has been demonstrated to confer a competitive advantage to the host organism it has invaded,” said study co-first author Erica Birkholz, PhD, a postdoctoral scholar in the Department of Molecular Biology. “Understanding that selfish genetic elements are not always purely ‘selfish’ has wide implications for better understanding the evolution of genomes in all kingdoms of life.”
In the new study, which focused on investigating “jumbo” phages, the researchers analyzed the dynamics as two phages co-infect a single bacterial cell and compete against each other. The researchers looked closely at the endonuclease, an enzyme that serves as a DNA cutting tool. The endonuclease from one phage’s mobile intron, the studies showed, interferes with the genome of the competing phage. The endonuclease therefore is now regarded as a combat tool since it has been documented cutting an essential gene in the competing phage’s genome. This sabotages the competitor’s ability to appropriately assemble its own progeny and reproduce.
“We were able to clearly delineate the mechanism that gives an advantage and how that happens at the molecular level,” said Biological Sciences graduate student Chase Morgan, the paper’s co-first author. “This incompatibility between selfish genetic elements becomes molecular warfare.”
The results of the study are important as phage viruses emerge as therapeutic tools in the fight against antibiotic-resistant bacteria. Since doctors have been deploying cocktails of phage to combat infections in this growing crisis, the new information is likely to come into play when multiple phages are implemented. Knowing that certain phages are using 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 Biological Sciences professor Joe Pogliano, PhD. “Understanding how they compete with one another will allow us to make better cocktails for phage therapy.”
