Resurrecting Dinosaur-Age Proteins To Cure Human Disease

While dinosaurs have not yet been resurrected Jurassic Park-style, scientists fiddling with ancient DNA sequences have made a discovery that may turn out to be a tad more useful: a treatment for gout. That a 90 million-year-old protein could treat a modern disease is a fascinating window into evolutionary history.

If you've heard of gout, you may know it as a "king of diseases." Those who have suffered through the disease's swollen and painful joints include Charlemagne, Henry VIII, and Benjamin Franklin—in short, the wealthy who could afford to eat and drink too much. Overindulgence can lead to the disease, but that's not the only biological cause for gout.

The ultimate reason humans are susceptible is, as Ed Yong lays out, "the legacy of evolutionary changes that took place more than 20 million years ago, which we're still paying for now." Gout is caused by a buildup of uric acid. Unlike other mammals, however, apes and their relatives don't have a functional gene for uricase, the protein that gets rid of the toxic molecule. Over millions of years, the DNA sequence for the uricase gene in apes had so became riddled with mutations as to be useless, like a piece of text so filled with typos it's illegible.

How to Resurrect a Bygone Protein

To figure out why this happened, scientists did some molecular paleontology. By comparing the differences between DNA sequences for uricase in modern mammals, scientists can go backwards, inferring what the uricase of their most recent common ancestor looked like. (The same technique has also been used to study hormone receptors.) Then they actually made the ancient proteins—or, rather, they put the DNA sequence into E. coli that translated ancient DNA into protein. This is how you resurrect a prehistoric protein.

With several different uricases of varying ancientness in hand, the scientists tested how well each protein worked on getting rid of uric acid. The best one was the oldest, which, at 90 million years old existed, at a time when dinosaurs still roamed the earth. Given the timing of when the uricase sequence then starting degrading, the researchers suspect it involves the rise of fruit in our ancestor's diets, which you can read about in detail here.

Resurrecting Dinosaur-Age Proteins To Cure Human Disease

Structure of the ancient uricase protein. Kratzer et al. PNAS.

But I want to go back to the idea of protein resurrection. The research team has since filed a patent on the ancient uricases and started a company to make the drug, according to Yong. Current gout treatments use uricases derived from pigs and baboons, but the ancient seems to work better in rat experiments so far. As these things go, it'll be a long while before FDA approval even if everything works.

Bringing Viruses Back To Life In Our Own DNA

For me, someone who is admittedly more enamored of biology than the average person, this is a fascinating example of how DNA is history. At the same time that the DNA in our cells is a roadmap for our bodies and the bodies of our future children, it is also a record of the evolutionary past, riddled with scars that tell a story.

We can even resurrect viruses hidden in our DNA. Incredibly, 8 percent of human DNA actually comes from viruses, which insert their DNA sequences into our cells as part of their initial viral strategy. There, some have remained as molecular fossils—until scientists dug them up to resurrect in the lab. A virus the world hasn't seen in millions of years can be found in and reconstructed right from our DNA. It can be mind-boggling to truly consider how much history is contained in every one of our microscopic cells. [PNAS via Not Exactly Rocket Science]

Top image: A foot swollen with gout. Hellerhoff/Wikimedia Commons