BY FAZALE RANA – AUGUST 17, 2016
Over the years I’ve learned that flexibility is key to a happy and successful life. If you are too rigid, it can create problems for you and others and rob you of joy.
Recently, a team of collaborators from Duke University and several universities in the US discovered that DNA displays unexpected structural flexibility. As it turns out, this property appears to be key to life.1 In contrast, the researchers showed that RNA (DNA’s biochemical cousin) is extremely rigid, highlighting another one of DNA’s unique structural properties that make it ideal as the cell’s information storage system.
To appreciate DNA’s uniquely optimal properties, a review of this important biomolecule’s structure is in order.
DNA consists of two chain-like molecules (polynucleotides) that twist around each other to form the DNA double helix. The cell’s machinery forms polynucleotide chains by linking together four different sub-unit molecules called nucleotides. DNA is built from the nucleotides: adenosine, guanosine, cytidine, and thymine, famously abbreviated A, G, C, and T, respectively.
In turn, the nucleotide molecules that make up the strands of DNA are complex molecules, consisting of both a phosphate moiety, and a nucleobase (either adenine, guanine, cytosine, or thymine) joined to a 5-carbon sugar (deoxyribose). (In RNA, the five-carbon sugar ribose replaces deoxyribose.)
Image 1: Nucleotide Structure
The backbone of the DNA strand is formed when the cell’s machinery repeatedly links the phosphate group of one nucleotide to the deoxyribose unit of another nucleotide. The nucleobases extend as side chains from the backbone of the DNA molecule and serve as interaction points (like ladder rungs) when the two DNA strands align and twist to form the double helix.
Image 2: The DNA Backbone
When the two DNA strands align, the adenine (A) side chains of one strand always pair with thymine (T) side chains from the other strand. Likewise, the guanine (G) side chains from one DNA strand always pair with cytosine (C) side chains from the other strand.
When the side chains pair, they form cross bridges between the two DNA strands. The length of the A-T and G–C cross bridges is nearly identical. Adenine and guanine are both composed of two rings and thymine (uracil) and cytosine are composed of one ring. Each cross bridge consists of three rings.
When A pairs with T, two hydrogen bonds mediate the interaction between these two nucleobases. Three hydrogen bonds accommodate the interaction between G and C. The specificity of the hydrogen bonding interactions accounts for the A-T and G-C base-pairing rules.
Image 3: Watson-Crick Base Pairs
Watson-Crick and Hoogsteen Base Pairing
In DNA (and in RNA double helixes), the base pairing interactions occur at precise locations between the A and T nucleobases and the G and C nucleobases, respectively. Biochemists refer to these exacting interactions as Watson-Crick base pairing. However, in 1959—six years after Francis Crick and James Watson published their structure for DNA—a biochemist named Karst Hoogsteen discovered another way—albeit, rare—that the A and T nucleobases and the G and C nucleobases pair, called Hoogsteen base pairing.
Hoogsteen base pairing results when the nucleobase attached to the sugar rotates by 180°. Because of the dynamics of the DNA molecule, this nucleobase rotation occurs occasionally, converting a Watson-Crick base pair into a Hoogsteen base pair. However, the same dynamics will eventually revert the Hoogsteen base pair to a Watson-Crick pairing. Hoogsteen base pairs aren’t preferred because they cause a distortion in the DNA double helix. For a “naked” piece of DNA in a test tube, at any point in time, about 1 percent of the base pairs are of the Hoogsteen variety.
Image 4: Watson-Crick and Hoogsteen Base Pairs
Image Credit: Wikimedia Commons
While rare in naked DNA, biochemists have recently discovered that the Hoogsteen configuration occurs frequently when: 1) proteins bind to DNA; 2) DNA is methylated; and 3) DNA is damaged. Biochemists now think that Hoogsteen base pairing is important to maintain the stability of the DNA double helix, ensuring the integrity of the information stored in the DNA molecule.
According to Hashim Al-Hashimi, “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.”2
It looks like the capacity to form Hoogsteen base pairs is a unique property of DNA. Al-Hashimi and his team failed to detect any evidence for Hoogsteen base pairs in double helixes made up of two strands of RNA. When they chemically attached a methyl group to the nucleobases of RNA to block the formation of Watson-Crick base pairs and force Hoogsteen base pairing, they discovered that the RNA double helix fell apart. Unlike the DNA double—which is flexible—the RNA double helix is rigid and cannot tolerate a distortion to its structure. Instead, the RNA strands can only dissociate.
It turns out that the flexibility of DNA and the rigidity of RNA is explained by the absence of a hydroxyl group in the 2’ position of the deoxyribose sugar of DNA and the presence of the 2’ hydroxyl group on ribose sugar of RNA, respectively. The 2’ position is the only structural difference between the two sugars. The presence or absence of the 2’ hydroxyl group makes all the difference. The deoxyribose ring can more freely adopt alternate conformations (called puckering) than the ribose ring, leading to differences in double helix flexibility.
Image 5: Difference between Deoxyribose and Ribose
This difference makes DNA ideally suited as an information storage molecule. Because of its ability to form Hoogsteen base pairs, the DNA double helix remains intact, even when the molecule becomes chemically damaged. It also makes it possible for the cell’s machinery to control the expression of the genetic information harbored in DNA through protein binding and DNA methylation.
It is intriguing that DNA’s closet biochemical analogue lacks this property.
It appears that DNA has been optimized for data storage and retrieval. This property is critical for DNA’s capacity to store genetic information. DNA harbors the information needed for the cell’s machinery to make proteins. It also houses the genetic information passed on to subsequent generations. If DNA isn’t stable, then the information it harbors will become distorted or lost. This will have disastrous consequences for the cell’s day-to-day operations and make long-term survival of life impossible.
As I discuss in The Cell’s Design, flexibility is not the only feature of DNA that has been optimized. Other chemical and biochemical features appear to be carefully chosen to ensure its stability; again, a necessary property for a molecule that harbors the genetic information.
Optimized biochemical systems comprise evidence for biochemical intelligent design. Optimization of an engineered system doesn’t just happen—it results from engineers carefully developing their designs. It requires forethought, planning, and careful attention to detail. In the same way, the optimized features of DNA logically point to the work of a Divine engineer.
“DNA Soaks Up Sun’s Rays” by Fazale Rana (Article)
The Cell’s Design by Fazale Rana (Book)
“The Cell’s Design: The Proper Arrangement of Elements” by Fazale Rana (Podcast)
- Huiqing Zhou et al., “m1A and m1G Disrupt A-RNA Structure through the Intrinsic Instability of Hoogsteen Base Pairs,” Nature Structure and Molecular Biology, published electronically August 1, 2016, doi:10.1038/nsmb.3270.
- Duke University, “DNA’s Dynamic Nature Makes It Well-Suited to Serve as the Blueprint of Life,” Science News (blog), ScienceDaily, August 1, 2016, www.sciencedaily.com/releases/2016/08/160801113823.htm.