URI biologists aim to find what it takes for species to escape the parasitic lifestyle

With a grant from the National Science Foundation, researchers will work to understand how a group of species managed to go from parasite to benign companion.

KINGSTON, RI. – February 1, 2023 – Single-celled creatures known as Nephromyces come from a long line of parasites—the same line, in fact, as the microorganism that causes malaria. But with a little help from some friends—namely a group of bacteria that help to perform some key metabolic functions—Nephromyces species managed to escape the parasitic lifestyle. With a new grant from the National Science Foundation, researchers from the University of Rhode Island will work to understand how this giant evolutionary leap occurred.

“I’ve always been interested in major evolutionary transitions,” said Christopher Lane, chair of the Department of Biological Sciences at URI and principal investigator on the grant. “Once species have evolved to be parasitic, changing that course is actually quite a difficult thing to do. So this work is about understanding the details of how that could happen.”

Single-cell Nephromyces seen under a microscope.

Nephromyces are an exceedingly odd group of creatures. They live exclusively inside sea grapes, marine filter-feeders commonly found along the East Coast of the United States. More specifically, they inhabit a bladder-like organ inside the sea grape called a renal sac, where they survive by breaking down and consuming the waste products sequestered there.

Scientists first documented Nephromyces about a century ago. 

“Someone opened one of these sacs, looked at it and said, ‘There’s something weird in here. It’s living, but we don’t know what it is,’” Lane said. 

The creatures were initially thought to be a fungus, but modern DNA testing showed them to be nothing of the sort. They turned out to be an apicomplexan, a phylum consisting almost exclusively of parasites, including the organisms that cause malaria, toxoplasmosis, and other illnesses. But unlike their apicomplexan brethren, Nephromyces aren’t parasitic. Parasites do damage to their hosts in some way. But essentially all wild sea grapes that have a renal sac also have Nephromyces without suffering any ill effects. And lab-grown sea grapes are perfectly healthy whether they’re infected or not. That means Nephromyces are commensalists—creatures that benefit from a relationship with a host without doing any harm (or good) to the host in the process. 

Lane and his colleagues are working to figure out how Nephromyces ended up on the evolutionary path out of parasitism—a somewhat rare and difficult transition. 

“When you live the parasitic lifestyle, you end up losing a lot of metabolic pathways,” Lane said. “You’re picking up end products from the host, so you don’t need to maintain those pathways. That makes going back on your own again quite difficult, because now you don’t have the metabolic pathways for amino acid biosynthesis and other key biological functions like that.”

One aspect of how Nephromyces escaped parasitism is already known. In the 1990s, a biologist named Mary Beth Saffo, with whom Lane has collaborated, discovered that Nephromyces are chronically infected with bacteria that help to perform some of those metabolic functions that may have been lost in the organism’s parasitic past. But things got a bit more complicated as Lane and his colleagues attempted to fully sequence the Nephromyces genome. 

“We thought we’d sequence the contents of one renal sac, and we’d be all set,” Lane said. “But when we got the data back, it was a mess. There was all this stuff that didn’t assemble well. The reason was that we had actually sequenced 17 different but closely related species.”

To make things even more complicated, they found that different Nephromyces species also have different bacterial endosymbionts, each performing different metabolic functions. But each Nephromyces species needs more than just its own endosymbiont to survive. It turns out that the different Nephromyces species need each other. 

“One individual species, even with its endosymbiont, doesn’t have all the metabolic pathways they need to get by,” Lane said. “But if you get pairs of species together, or even better, triplicates of different species that each have different endosymbiotic bacteria, then they complete all the pathways that they need. It’s a really weird system.”

With this new grant, Lane hopes to explain how all these moving parts came together to extricate Nephromyces from parasitism. One of the keys to doing that is to figure out just how many Nephromyces species there actually are, along with how many bacterial pals they have. In addition to the dozen or so his team has already documented, Lane says there are indications that many, many more are out there undiscovered. 

Lane and his team will sequence DNA from sea grape renal sacs collected all along the Eastern and Southern coasts of the U.S. Once they have a sense of how many species there are, and how each interacts with different bacterial species, they can start to reverse engineer the process by which Nephromyces diverged from its parasitic relatives. 

“There are roughly 6,000 apicomplexan species, and they’re all parasites,” Lane said. “Then along comes Nephromyces in the middle of all this, and they’re doing something completely different. So we hope to better understand what makes a parasite by learning what breaks parasitism, and we can do that by looking at this weird exception to the rules.”

It also means that Lane and his team will have lots of new species to name. 

“We’ve committed in the grant to name 60 nephromyces species and 60 bacteria species, but that might just be scratching the surface,” Lane said. “I’m not sure how we’re going to come up with all the names, but we’ll figure it out.”