Scientists discover Borgs, DNA strands that assimilate genes from their hosts

In 2018, Jillian Banfield’s lab went digging in the mud for viruses that infect bacteria. While analyzing the samples they brought back to the lab, the geomicrobiologist at University of California, Berkeley found something much weirder: unusually large pieces of DNA chock full of mysterious genes, many of them new to science, and others seemingly poached from a kind of methane-eating microbe. By studying the genetic fingerprints in these extrachromosomal DNAs, Banfield deduced that they were assimilating genes from other organisms, particularly archaea, a large group of microbes distinct from bacteria.

When Banfield excitedly explained the research at Thanksgiving last year, her son said, “Mum, they’re Borgs”—a reference to the cybernetic alien race in Star Trek that conquers other species and assimilates their biology and technology. The name stuck.

In a preprint study, which has not yet undergone peer-review, Banfield’s lab describes the discovery of at least 19 unique Borgs found between 1 cm and 6 m underground (bioRxiv 2021, DOI: 10.1101/2021.07.10.451761). Many of these Borgs were extracted from the mud of seasonal wetlands called vernal pools, including one in Banfield’s backyard. She thinks Borgs are likely residing within Methanoperedens, a kind of anaerobic archaea that metabolizes methane.

The study has sent microbiologists into a tizzy. Many are thrilled that something so novel could be found in the dirt. “These things could be all over the place and we’ve been missing them until now,” says Jennifer Glass, a geomicrobiologist at the Georgia Institute of Technology. Others doubt that Banfield’s Borgs are a unique enough kind of extrachromosomal DNA to warrant a new name. Nonetheless, some researchers are already imagining how Borgs could be used to reduce methane emissions in agriculture, or transport large stretches of DNA into cells in biotechnology applications.

Extrachromosomal DNA itself is not a new discovery. For example, many bacteria use circular pieces of DNA called plasmids to hold genes that make them resistant to antibiotics or help them survive changing environments. These plasmids can be shared between bacteria when they are needed and shed when they are no longer useful.

But Banfield says the Borgs are unique for several reasons, including their immense size. Many range from about 660,000 to 1.1 million base pairs and appear to carry clusters of genes encoding entire metabolic complexes—particularly methane oxidation. Plasmids, in contrast, are often much smaller, typically encoding one or a few key proteins. It’s like the difference between instructions for the whole engine, versus a piston. Banfield also found that the proportion of guanine and cytosine bases in the linear DNA was markedly different from that in the host’s circular chromosomes. The discrepancy between those genetic fingerprints suggest that the extrachromosomal DNA contained genes recently acquired from other organisms.

Mart Krupovic, an archaeal virologist at the Pasteur Institute, says the discovery of Borgs “is wonderful for the archaeal community,” but he is skeptical about their novelty. Streptomyces bacteria have giant linear plasmids hundreds of thousands to more than one million base pairs long. Krupovic thinks that Borgs are better described as a kind of giant plasmid, sometimes called megaplasmids. “I don’t have any issues with how they did the work,” he says, adding that making this discovery in an organism that can’t even be grown in the lab “is not trivial.”

Banfield concedes that there is nothing “absolutely unique” about the structure of Borgs, but she also thinks that Borgs have enough unusual features that together make them distinct from plasmids, viruses, and other known kinds of extrachromosomal DNA.

Alyson Santoro, a marine microbial ecologist at University of California, Santa Barbara, is convinced that Borgs are real, “but like any good discovery, it raises as many questions as it answers,” she says.

Santoro is curious to know what the methane oxidation genes on the Borg do compared to the similar genes in the archaea genome. “That would be the next step after this paper.” More fundamentally, she also wonders whether Borgs are shared between organisms, and if so, how. And since Methanoperedens is a relatively narrow branch on the archaeal tree of life, it will be interesting to see if other archaea have Borgs too. There could be overlooked Borg DNA in public or private databases hiding in plain sight, she adds. “Now that this paper is out, people will go back to their datasets.”

About 20% of the Borg genes appeared to come from Methanoperedens, including genes for methane metabolism. The other 80% were new to science, and Banfield says she is “positive” there’s some interesting biology to uncover.

The Borgs also have several regions of code each with a different sequence of repetitive DNA. Banfield doesn’t know what these regions do, but she is eager to find out. CRISPR, which Banfield knows well, is a microbial immune system made of regions of repetitive genetic code interspersed with unique DNA sequences. In 2006, Banfield introduced Berkeley scientist Jennifer Doudna to CRISPR, setting the stage for Doudna’s invention of CRISPR gene editing, for which she won the 2020 Nobel Prize in Chemistry.

The two Berkeley scientists continue to work together, and the new Borg study was helmed by Basem Al-Shayeb, a PhD student who works in both Banfield’s and Doudna’s labs. The study garnered attention when Banfield posted it on Twitter and said she hasn’t “been this excited about a discovery since CRISPR.”

“CRISPR was pretty darn exciting, so it was a high bar to pass,” she tells C&EN. To her, Borgs are exciting for their genetic uniqueness, for how much remains to be learned about them, and for their potential environmental implications. “These things are huge, they are complex, and they have methane metabolism—and that is a huge, huge issue for climate change.” Banfield says that she is planning to discuss future work on Borgs, and potential applications of the discovery, with Doudna.

Banfield already has at least one idea for practical applications of Borgs: reducing methane emissions in agriculture. Rice paddies, in particular, are huge sources of methane, thanks to the methane-producing archaea that thrive around their roots. Banfield’s group and scientists at the Innovative Genomics Institute at Berkeley plan to look for Borg-laden Methanoperedens that can live peacefully alongside rice roots and feast on the methane there before it rises to the surface. Further in the future, Banfield says scientists may even consider adding Borgs, or reduced versions with the most important genes, to other organisms to help cut methane emissions even further.

“In the future, if we were able to actually somehow enhance anaerobic methane oxidation in systems, that would help tremendously in terms of decreasing carbon in the atmosphere,” says Stephanie Yarwood, a microbial ecologist at the University of Maryland. “But I don’t know if we will get there anytime soon.”

Michael Fischbach, a chemist and microbiologist at Stanford University, looks forward to future studies demonstrating that the methane metabolism genes on Borgs are actually active. That could be proven by either transferring the Borgs to an organism that doesn’t oxidize methane, and seeing if they gain the ability, or by using gene editing to ablate the Borg genes in Methanoperedens and seeing if it reduces the microbe’s methane-eating ability. “It is not trivial to do, but we will all want to see that. It will be a Rubicon to cross.”

If Borgs can be shared between organisms, it raises the possibility of using them for genome augmentation, the process of adding new capabilities to cells, Fischbach says. “For anybody who is interested in genome editing and genome engineering it is hard to think of something cooler than dropping a million base pairs of code into a genome that makes it possible to eat methane. That’s ultracool.”