DNA is the molecule that contains the genetic information in all living organisms. It is made up of two strands that wrap around each other in a double helix structure. The two strands are held together by bonds between nucleotide bases on each strand. Adenine (A) bonds with thymine (T) and cytosine (C) bonds with guanine (G).
The chirality of DNA
An interesting property of DNA is its chirality or “handedness”. The two strands of the double helix are not identical, but are mirror images of each other. This means that DNA is a chiral molecule. Chiral molecules come in two non-superimposable mirror image forms called enantiomers. Enantiomers have identical physical properties except for their rotation of plane polarized light. One enantiomer rotates light clockwise, while the other rotates light counterclockwise. The clockwise enantiomer is designated as (+) or d for dextrorotatory. The counterclockwise enantiomer is designated as (-) or l for levorotatory. For DNA, the predominant enantiomer found in nature is the right-handed double helix, designated as the d form.
Enantiomers of DNA
The two enantiomers of DNA are:
- d-DNA – Right-handed double helix
- l-DNA – Left-handed double helix
In d-DNA, the strands twist in a clockwise direction as they wind around each other. In l-DNA, the strands follow a counterclockwise path. Although both forms are possible, right-handed d-DNA predominates in most organisms. Next, we’ll look at some of the theories for why nature favors d-DNA.
Theories for predominance of right-handed DNA
There are several theories proposed to explain the preference for right-handed DNA in organisms:
1. Energetics theory
The predominant right-handed form may be more thermodynamically stable and lower in energy. Calculations indicate d-DNA is more stable than l-DNA by about 3-5 kJ/mol due to favorable base stacking interactions. The lower energy state makes d-DNA the more naturally abundant form.
2. Chiral selection theory
Interactions between DNA and chiral molecules such as proteins and sugars may have driven a preference for the right-handed form early in evolution. Most amino acids are left-handed while sugars are right-handed. Binding interactions between these chiral molecules and DNA may have helped select for the right-handed d-DNA.
3. Helicase unwinding theory
DNA helicases are enzymes that unzip and unwind the DNA double helix during replication and transcription. Most helicases move unidirectionally along DNA while unwinding it. They preferentially unwind DNA with a handedness matching the directionality of their movement. Since most helicases move along DNA and unwind it in a rightward direction, they would thus drive a preference for right-handed DNA.
4. Circular DNA theory
Some researchers propose that an ancestral form of circular DNA drove preference for the right-handed state. When circular DNA is supercoiled, a right-handed double helix is more favorable. Supercoiling of early circular plasmids and genomes may have led to selective pressure for right-handed DNA.
Evidence for preference of right-handed DNA
There are several key lines of evidence indicating nature strongly favors right-handed DNA:
- The vast majority of sequenced DNA from organisms is in the right-handed B-form structure.
- Left-handed Z-form DNA only forms in very specific repeat sequence regions under high salt conditions.
- Efforts to synthesize left-handed DNA yield primarily right-handed DNA due to spontaneous conversion.
- Left-handed DNA is unstable and converts to the more favorable right-handed form over time.
Together, this evidence indicates enzymes and processes in cells strongly drive DNA into the right-handed double helical structure.
DNA in the B-form structure is right-handed
Under normal cellular conditions, genomic DNA forms the canonical B-form right-handed double helix. X-ray diffraction and spectroscopy studies consistently find DNA in cells exists primarily in the d-DNA B-form configuration. This demonstrates nature’s strong preference for the right-handed structure for encoding genetic information.
Left-handed Z-DNA is a rare alternative form
The left-handed Z-DNA form only occurs at specific repeat sequence regions of the genome when high salt concentrations stabilize it. These are unusual environmental conditions not generally found inside cells. Therefore, observation of some left-handed Z-DNA at a few genomic sites does not overcome the preference for B-form right-handed DNA under physiological conditions.
Chemical synthesis results in right-handed DNA
Efforts to chemically synthesize left-handed l-DNA result in spontaneous conversion primarily to the right-handed d-form. Even starting with entirely left-handed DNA, it rapidly converts to favor the more stable right-handed configuration. This demonstrates the challenge in artificially making left-handed DNA that does not naturally want to exist in that form.
Left-handed DNA is unstable
In vitro experiments show left-handed DNA is kinetically unstable. When starting with pure l-DNA, it spontaneously isomerizes and converts to the more favorable right-handed form over hours to days. This instability of the left-handed structure further illustrates nature’s preference for the right-handed DNA form.
Biological consequences of right-handed DNA
The use of primarily right-handed DNA in organisms has several important consequences:
- Allows complementary base pairing between the strands
- Provides a uniform substrate for replication and transcription enzymes
- Produces optimal geometry for binding of regulatory proteins
- Generates torsional strain that can regulate DNA metabolic processes
Complementary base pairing
The uniform right-handed structure is key for the specific A-T and G-C base pairing between the strands that provides sequence specificity. The complementary base pairs are oriented to pair through hydrogen bonding at optimal geometry in the right-handed form.
DNA-protein interactions
Consistent use of right-handed DNA provides the optimal binding surfaces and grooves for interaction with replication, transcription, and regulatory proteins that act upon the DNA. A uniform substrate enables specific and efficient DNA-protein interactions.
Torsional strain
Coiling of the right-handed double helix generates torsional strain when the DNA is underwound or overwound. This torsional strain can be harnessed to regulate dynamic DNA processes like replication or transcription that involve unwinding of the double helix.
Remaining mysteries about DNA handedness
While we now understand nature’s preference for right-handed DNA, some open questions remain:
- Does left-handed DNA serve any functional roles? Or is it simply an unavoidable structural consequence?
- Can chiral interactions fully explain the initial emergence of right-handed DNA?
- How did right-handed DNA first arise – was there a racemic mixture followed by selective pressure?
- Are there undiscovered conditions that might stabilize left-handed DNA inside cells?
Further research into the structural transitions and capabilities of DNA will shed light on these remaining questions about the origins of its handedness.
Conclusion
In summary, right-handed DNA predominates in nature due to its favorable energetics, interactions with chiral molecules, unwinding by helicases, and behavior of circular DNA. The uniform right-handed structure provides complementary base pairing, optimal protein binding, and useful torsional strain. While some mysteries remain about the origins of DNA’s chiral preference, ongoing research continues to reveal the importance of its right-handed double helical structure for biological function.
