Hydra DNA Reveals There’s More Than One Way to Regrow a Head

In rivers and streams across the globe lives a tube-shaped carnivore. It paralyzes and captures prey with a crown of tentacles, then draws it in through its mouth (which also serves as its anus). This unsettling creature is a hydra, a freshwater-dwelling cnidarian no more than a half-inch long that eats mostly insect larvae and crustaceans. A hydra’s appearance and eating habits alone give it a sci-fi feel, but its ability to regenerate its body — even its head — from only a scrap of tissue or pile of cells raises it to another level.

“It’s one of these organisms that’s thought to never die unless you try to kill it or, you know, starve it to death,” Ali Mortazavi, a developmental biologist at the University of California, Irvine, said. A hydra’s regenerative abilities allow it to constantly replace bits of itself, so it doesn’t succumb to things like old age or disease. Aside from the immortality perk, constant regeneration means a hydra doesn’t have to sweat the small stuff, like losing body parts. Give it a few days and it will grow back anything.

Dr. Mortazavi and his colleagues have taken a big step in understanding how a hydra regenerates its head. Their research was published in Genome Biology and Evolution on Wednesday.

To investigate what makes this remarkable feat possible, the researchers looked at changes in gene expression — whether a gene is copied from DNA into RNA — throughout the course of hydra head regeneration. This control of gene expression is called epigenetic regulation. Hydras have a genome quite similar to that of species with little regenerative capacity, like humans, so it’s thought that epigenetic regulation plays a major role in making the hydra’s powers of regeneration possible.

The team discovered dynamic alterations in the regulation of stretches of DNA called enhancers. Enhancers increase the likelihood that a related gene will be copied from DNA into RNA. These enhancers were helping to ensure the expression of many genes, the team found, including those long known to be important for regeneration. “Nobody knew hydras had these enhancer regions,” said Dr. Mortazavi, who noted that the study put hydra in the same club as many other animals, including mammals.

An almost fully developed hydra polyp about to bud off. Researchers discovered that while hydras grow new heads during regeneration as well as asexual reproduction, they use different processes for each.Credit…Anna Klompen/University of Kansas

The researchers then compared gene expression during head regeneration with gene expression during budding, a form of asexual reproduction where a hydra grows a polyp that is basically a copy of itself. That process requires growth of a second head, but the researchers found that a budding head forms in a very different way from a head regrowing after injury.

“When I took a look at the trends in gene expression, the genes are kind of increasing slowly throughout the budding head development, but in regeneration, we noticed these sharp turns,” said ​Aide Macias-Muñoz, a developmental biologist at University of California, Santa Barbara, who was one of the study authors. “A lot of genes are being turned on and then turned off and then turned back on. So even though the end result is the same, it looks like the trajectory is actually very different.”

Dr. Mortazavi was also surprised to find that gene expression timing varied so much between head regeneration and budding. “Clearly there’s more than one way to make a head,” he said.

The discovery of these enhancer regions and their role in hydra head regeneration also suggests that the evolution of enhancers predates the evolutionary divergence of cnidarians and bilaterians (animals with bilateral symmetry, like humans) around 750 million years ago. Erin Davies, a developmental biologist at the National Cancer Institute who studies regeneration but was not involved in the work, sees these findings as a reminder of the importance of studying ancient creatures like hydras.

“They are really in a prime position for answering a lot of very fundamental questions in developmental biology,” she said, including “How did nervous systems evolve? How did you get bilateral symmetry?”

This kind of work is also essential for the regenerative medicine field, Dr. Davies said, where a common goal is to restore diseased and injured tissues or even whole organs.

“If you have a good handle on a paradigm in any animal system,” she said, “then you can start to think about how you might reverse engineer things in less regeneration-competent species, like mammals.”

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