Left to right: Pea aphid, by Shipher Wu; rice fungus by Forrest O; spikemoss by Luis Fernández García
Left to right: Pea aphid, by Shipher Wu; rice fungus by Forrest O; spikemoss by Luis Fernández García

How An Antibiotic Gene Jumped All Over The Tree of Life

Every living thing on the planet has to contend with bacteria. To many viruses, they are prey. To other bacteria, they are competitors. To animals and plants, they can be the cause of devastating diseases or beneficial partners that provide everything from nutrition to immunity to light. They have been around for some 3 billion years, and they are everywhere. So, it makes sense that a gene which allows its owners to deal with bacteria might find a home throughout the entire tree of life.

That’s what Jason Metcalf and colleagues from Vanderbilt University have now discovered. They tracked a gene called GH25-muramidase, which makes an enzyme that can break apart a bacterium’s outer wall. It’s common in bacteria, which use it to remodel themselves and reproduce by dividing in two. But Metcalf showed that it has also jumped from bacteria into every other major branch of life. It’s in animals, plants, fungi, archaea, and even some viruses.

There are many similarly universal genes, which were present in the last common ancestor of all living things, and were passed down from parent to offspring. But GH25-muramidase is different. It arose in bacteria and then jumped horizontally into other kingdoms. “It has been co-opted by different domains of life to be used as an antibacterial weapon,” says Seth Bordenstein, who led the study.

I’ve written about these horizontal gene transfers a lot (here’s the latest piece from just last week). But this example stands out for its promiscuity. Genes hop between bacteria all the time, carrying traits like antibiotic resistance with them. There are also several examples of genes jumping from bacteria to animals, from bacteria to archaea, from animals to animals, and every other combination you can think of. But there are very few examples of genes that have moved everywhere. There are clearly highways of gene traffic that connect every branch of the tree of life, but very few genes have taken the complete roadtrip.

Why? Horizontal gene transfers aren’t always a good thing; maybe they often aren’t. The genes could be harmful in the wrong host, or might disrupt important genes. So even if jumps happen, they might get quickly purged by natural selection. If that’s the case, only genes with universal appeal would have universal presence.

That’s what Bordenstein’s team found. They initially studied a virus that attacks Wolbachia—a extremely cool and successful bacterium that infects around two-thirds of insect species. They found that the virus kills Wolbachia using GH25-muramidase, and then searched for this gene in the sequenced genomes of other species. To their surprise, they found it all over the place: in many different bacteria; the plant-sucking pea aphid; the ancient spikemosses (a group of plants); fungi that infect rice; and Aciduliprofundum boonei, an archaeon that lives in hot, belching, deep-sea vents. (Archaea are one of the three great domains of life.)

Metcalf compared GH25-muramidase in all of these species to reconstruct its evolutionary history. And he found that the family tree of the different versions didn’t look anything like the family tree of their owners—a clear sign of horizontal jumps from one group to another. Also, the aphid is the only insect that has this gene, and the spikemosses are the only plants that do. This also suggests that they got it horizontally from some bacterium, rather than vertically from their ancestors.

In fact, the archaea, fungi, spikemosses, and viruses all inherited their copies of GH25-muramidase from different groups of bacteria. In each case, the donor and recipient are neighbours. The archaeon got its copy from one of the Firmicutes, a group that often colonises deep-sea vents. The spikemoss got its copy from Actinobacteria, which lord over soil communities. And both the aphid and the Wolbachia viruses seem to have picked up their copies from Proteobacteria, which are often found in the bodies of insects.

But the team was especially interested in the archaeon, A.boonei. Archaea build their cell walls using different molecules than bacteria, so they are immune to GH25-muramidase. Instead, the team showed that A.boonei can use its borrowed gene as a weapon against its bacterial neighbours. Its version can kill many different bacteria, especially those that live in the same deep-sea vents. And when the team grew A.boonei alongside with one of those vent bacteria, it churned out large amounts of GH25-muramidase and outnumbered its competitor. A.boonei won out, even though it is the slower grower of the two microbes.

“They cast the story in terms of competition,” says Bill Martin from Heinrich-Heine University in Dusseldorf. But since Aciduliprofundum eats other things, “maybe it is not so much carving out a competitor-free niche as helping itself to a bite of bacterium for lunch.”

The team acknowledge this possibility. And either way, the gene clearly allows the archaeon to do something to bacteria. That’s a first. Other groups have suggested that archaea might wield antibacterials, but no one had identified a specific gene before. This discovery suggests (with the usual caveats) that archaea might be a good source of new antibiotics, especially since they’re great at tolerating high temperatures and pressures.

It’s less clear how the borrowed gene benefits the other recipients. Metcalf’s team have tried to purify these other versions of GH25-muramidase but with no success. Still, based on their sequence, it certainly looks like they should also be able to target bacteria in the same way. And perhaps this explains why the gene has been so promiscuous. By imparting a universally useful trait, it proved to be a welcome immigrant into every corner of life.

And as David Baltrus from the University of Arizona points out, the team really only focused on a fragment of GH25-muramidase. “Not only has this motif been independently recruited by various [organisms], but it has been incorporated and elaborated into much larger proteins across species,” says Baltrus. In other words, different species have borrowed this basic bacterial tool and used it to fashion even more complex molecular machines.

“Horizontal gene transfer is widely recognized as a powerful force shaping evolution within bacterial populations but as more genomes are sequenced, it becomes increasingly apparent that its effects are not limited to microbes,” adds Baltrus.

Reference: Metcalf, Funkhouser-Jones, Brileya, Reysenbach & Bordenstein. 2014. Antibacterial Gene Transfer Across the Tree of Life. eLife. http://dx.doi.org/10.7554/eLife.04266