(The research was published on Nature Structural & Molecular Biology.)
A new study has shown for the first time that RNA – the older molecular cousin of DNA – splits apart when it tries to incorporate change, while DNA can contort itself and change its shape to compensate for any chemical damage.
The research could finally explain why the blueprint of life is made from DNA and not RNA – and it could also prompt a rewrite of the textbooks.
“For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game,” said lead researcher Hashim Al-Hashimi from the Duke University School of Medicine. “We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life.”
Back in 1953, Watson and Crick first published their model of the DNA double helix, and predicted how the base pairs – A & T and G & C – fit together.
You’re probably pretty familiar with that formation by now – two strands of DNA are linked up by the bonding of the base pairs, forming ladder rungs that hold together the twisted ladder of DNA.
But researchers struggled to find evidence that the base pairs were bonding in the way that Watson and Crick had predicted – something they called Watson-Crick base pairs. Then in 1959, biochemist Karst Hoogsteen managed to take a picture of an A–T base pair, showing a slightly more skewed geometry, with one base rotated 180 degrees relative to the other.
Since then, researchers have observed both Watson-Crick and Hoogsteen base pairs in images of DNA.
But five years ago, Al-Hashimi and the Duke team found something that had never seen before: DNA base pairs constantly morphing back and forth between Watson-Crick and the Hoogsteen bonding configurations. This adds a whole other dimension and level of flexibility to DNA’s structure.
It turns out that DNA appears to be using Hoogsteen bonding when there’s a protein bond to a DNA site – or if there’s chemical damage to any of its bases – and once the damage is fixed or the protein is released, the DNA goes back to Watson-Crick bonds.
That discovery was a big deal in itself, but now the team has shown for the first time that RNA doesn’t have this ability, which could explain something that scientists have puzzled over for years: why DNA forms the blueprint for life, not RNA.
So, while DNA will absorb chemical damage and adapt to work around it, RNA becomes too stiff and falls apart, making DNA the better structure to pass genetic information down between the generations.
“In DNA this modification is a form of damage, and it can readily be absorbed by flipping the base and forming a Hoogsteen base pair. In contrast, the same modification severely disrupts the double helical structure of RNA,” said one of the team, Huiqing Zhou.
“The finding will likely rewrite textbook coverage of the difference between the two purveyors of genetic information, DNA and RNA,” said a Duke University press release.
You can see DNA on the left performing Hoogsteen bonding to incorporate damaged base-pairs, while RNA on the right falls apart:
The researchers were able to figure this out by creating double-helices out of RNA and DNA, and using advanced imaging techniques to watch how its base pairs were bonding.
They were able to show that, at any one time, around 1 percent of the DNA bases were changing into Hoogsteen base pairs. But the same thing wasn’t seen in the RNA strands.
They tested more of these RNA double-helices under a whole range of conditions, but none of them ever seemed to change to Hoogsteen base pairs. They even forced RNA into forming these Hoogsteen base pairs just to see if it could happen, but as soon as they did, the RNA strands fell apart.
The team explains that this is because the RNA double helical structure is more packed together compared to DNA, and because of that, one RNA base can’t change direction without hitting another one or shifting atoms, and ripping the whole structure apart.
“There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn’t have the tools to see them, until now,” said Al-Hashimi.
Further research is needed to test the hypothesis that it’s this flexibility of DNA, and not RNA, that led to DNA becoming the blueprint of life, but if confirmed, it could help us understand why life on Earth evolved to be the way it is.
And it’s pretty cool that after all these years, we’re still learning new things about the molecules that make us who we are.
A brand new research has proven for the primary time that RNA – the older molecular cousin of DNA – splits aside when it tries to include change, whereas DNA can contort itself and alter its form to compensate for any chemical injury.
The analysis might lastly clarify why the blueprint of life is created from DNA and never RNA – and it might additionally immediate a rewrite of the textbooks.
“For one thing as elementary because the double helix, it’s superb that we’re discovering these primary properties so late within the recreation,” said lead researcher Hashim Al-Hashimi from the Duke College Faculty of Drugs. “We have to proceed to zoom in to acquire a deeper understanding relating to these primary molecules of life.”
Again in 1953, Watson and Crick first revealed their mannequin of the DNA double helix, and predicted how the bottom pairs – A & T and G & C – match collectively.
You are in all probability fairly conversant in that formation by now – two strands of DNA are linked up by the bonding of the bottom pairs, forming ladder rungs that maintain collectively the twisted ladder of DNA.
However researchers struggled to seek out proof that the bottom pairs have been bonding in the best way that Watson and Crick had predicted – one thing they referred to as Watson-Crick base pairs. Then in 1959, biochemist Karst Hoogsteen managed to take an image of an A–T base pair, displaying a barely extra skewed geometry, with one base rotated one hundred eighty levels relative to the opposite.
Since then, researchers have noticed each Watson-Crick and Hoogsteen base pairs in photographs of DNA.
However five years ago, Al-Hashimi and the Duke staff discovered one thing that had by no means seen earlier than: DNA base pairs continuously morphing forwards and backwards between Watson-Crick and the Hoogsteen bonding configurations. This provides an entire different dimension and degree of flexibility to DNA’s construction.
It seems that DNA seems to be utilizing Hoogsteen bonding when there is a protein bond to a DNA website – or if there’s chemical injury to any of its bases – and as soon as the injury is fastened or the protein is launched, the DNA goes again to Watson-Crick bonds.
That discovery was an enormous deal in itself, however now the group has proven for the primary time that RNA does not have this capability, which might clarify one thing that scientists have puzzled over for years: why DNA varieties the blueprint for all times, not RNA.
So, whereas DNA will take in chemical injury and adapt to work round it, RNA turns into too stiff and falls aside, making DNA the higher construction to move genetic info down between the generations.
“In DNA this modification is a type of injury, and it could actually readily be absorbed by flipping the bottom and forming a Hoogsteen base pair. In distinction, the identical modification severely disrupts the double helical construction of RNA,” said one of the team, Huiqing Zhou.
“The discovering will probably rewrite textbook protection of the distinction between the 2 purveyors of genetic info, DNA and RNA,” stated a Duke College press release.
The researchers have been capable of determine this out by creating double-helices out of RNA and DNA, and utilizing superior imaging methods to observe how its base pairs have been bonding.
They have been capable of present that, at anybody time, round 1 % of the DNA bases have been becoming Hoogsteen base pairs. However the identical factor wasn’t seen within the RNA strands.
They examined extra of those RNA double-helices beneath an entire vary of circumstances, however none of them ever appeared to vary to Hoogsteen base pairs. They even pressured RNA into forming these Hoogsteen base pairs simply to see if it might occur, however as quickly as they did, the RNA strands fell aside.
The group explains that it’s because the RNA double helical construction is extra packed collectively in comparison with DNA, and due to that, one RNA base cannot change course with out hitting one other one or shifting atoms, and ripping the entire construction aside.
“There’s a tremendous complexity constructed into these easy lovely buildings, entire new layers or dimensions that we have now been blinded to as a result of we did not have the instruments to see them, till now,” said Al-Hashimi.
Additional analysis is required to check the speculation that it is this flexibility of DNA, and never RNA, that led to DNA turning into the blueprint of life, but when confirmed, it might assist us perceive why life on Earth advanced to be the best way it’s.
And it is fairly cool that in any case these years, we’re nonetheless studying new issues concerning the molecules that make us who we’re.