By studying the atoms that make up each DNA molecule, Hashim Al-Hashimi, a biochemist at Duke University, thinks he may have found an answer: DNA is capable of shapeshifting in a way that RNA can't, he says in a new study in the journal Nature Structural and Molecular Biology. That makes DNA more resilient — and therefore a better repository of the code that makes us ourselves.
The secret to DNA's success, Al-Hashimi says, is something called a Hoogsteen base pair, which was discovered by biochemist Karst Hoogsteen in the 1960s. Don't worry if you don't recall hearing the term in your high school biology class — until recently, scientists struggled to capture the strange structure, and believed that it only cropped up on rare occasions.
But in 2011, Al-Hashimi and a team of other scientists took a look at DNA molecules in a nuclear magnetic resonance (NMR) machine that allows researchers to visualize what's going on at a molecular level. They found that the nucleic acid base pairs that make up the steps of DNA's spiral staircase are continually shifting between two forms. Most of the time, they're connected in the way described by James Watson and Francis Crick more than 50 years ago. But at any given moment, roughly 1 percent of all base pairs form a Hoogsteen pair, in which one of the nucleic acids is flipped 180 degrees, causing the entire double helix structure to kink.
"It becomes this very dynamic entity," Al-Hashimi said. "You can just imagine the molecule dancing around."
Often, Hoogsteen pairs arise when the DNA has been undermined in some way: Carcinogenic chemicals will attack DNA by adding a methyl group (one carbon bonded to three hydrogen atoms) to one of the two nucleic acids that comprise a base pair. Al-Hashimi compared this to hammering a wayward nail into a board that makes up half a step in a staircase. By flipping the nucleic acid over so the "nail" is no longer sticking out, the base pair can accommodate the damage.
Having found this phenomenon in DNA, Al-Hashimi wondered whether RNA, which also has a helix structure, would behave the same way. He and his colleagues added a methyl group to a strand of RNA to see what happened.
"It was like dropping a nuclear bomb on the helix," Al-Hashimi said. "Literally the whole helix started to unravel."
RNA molecules are incapable of forming Hoogsteen pairs, it turned out. So instead of shifting to accommodate damage, they fall apart.
"If our genomes were made up of RNA, there’s a very good chance that they wouldn’t be able to sustain chemical damage that’s inflicted on them all the time," Al-Hashimi said. "It seems like DNA's ability to absorb damage is one reason why we evolved DNA-based genomes."
This explanation is "still speculative," he noted, "since we can't travel back in time."
But it could explain how RNA got demoted from master plan to mere messenger when DNA took over. In modern cells, RNA reads the information inscribed in DNA and carries it to protein-production centers, which get to work according to DNA's directions. Looking at RNA in a NMR machine, Al-Hashimi noticed that adding a methyl group — and prompting the RNA strand to unravel — actually made it more efficient in this task.
"It seems that nature has exploited the inability of RNA to absorb damage to create this molecular switch," he said. "By methylating the RNA you can increase production of proteins."
There's a lot to be learned about this process — microscopes can't capture what's going in DNA on such a small scale, so it's hard to study.
"For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game," Al-Hashimi said in a statement. "We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life."