DNA: Nature’s own director of Life

Artwork with wire and thread depicting DNA and the human body in abstract form

What makes each life unique?

Cells are the basic units of life. One of  its major components is the nucleus, which contains DNA (deoxyribonucleic acid) -  the cell's hereditary material. DNA provides instructions for the cells to grow, mature, divide, die, thus serving as the cell’s command centre, akin to how the brain functions controlling  our body’s. Interestingly, it is because of the differences in one's DNA which accounts for all the variations seen within us and other lifeforms around us. 

 

Discovery of DNA structure

The history behind determining molecular structure of DNA is shown in Figure 1. In the 1950s, American biologist James Watson and English physicist Francis Crick were widely credited for discovering the double helical structure of DNA. However the idea of  double helix was stemmed by scientific discoveries sprouted from the 18th century (Figure 1). 

 

 

Timeline showing the DNA structure discovery.
Figure 1. Timeline showing the DNA structure discovery.

 

In 1919, Phoebus Levene proposed that nucleic acids are composed of a series of nucleotides made of nitrogen-containing bases (purines - A and G; Pyrimidines - C and T), a sugar molecule, and a phosphate group (Figure 2). These building blocks of DNA are linked together by covalent bonds between the (deoxy)ribose sugar of one nucleotide and the phosphate of the next nucleotide, constituting the sugar-phosphate backbone (Figure 3 blown-up view).

 

Image displaying the components of nucleic acids and their chemical structure
Figure 2: Components of nucleic acids and their chemical structure. (Image from Pray, L. 2008).

 

In the year 1950, an Austrian biochemist Erwin Chargaff made two major conclusions. (i) The DNA composition among species varies. The same nucleotides do not repeat in the same order. (ii) The amount of adenine (A) and the amount of guanine (G) in a DNA molecule is approximately equal to the amount of thymine (T) and the amount of cytosine (C), respectively (i.e., As=Ts; Gs=Cs). This rule has been described as “Chargaff's rule". 

 

Photograph 51

The famous X-ray diffraction image of DNA, used to determine its structure and widely known today as photograph 51, was taken by Raymond Gosling under the supervision of Maurice Wilkens and Rosalind Franklin in 1952. This picture clearly indicated that DNA is a helical structure (‘Xâ€� in the diffraction pattern), with a repeat of 10 units (reflected as layer lines) and repeat unit distance is 3.4Ã…, and the phosphates were on the outside of a helical structure. 

Watson and Crick obtained Franklin's X-ray diffraction data and used it in creating their 3D model of double-helix DNA. In 1962, they were awarded the Nobel Prize along with Maurice Wilkins for solving the structure of DNA. This was a historical milestone and gave rise to modern molecular biology. 

The major features of Watson-Crick double helical DNA model are (Figure 3):

  • DNA is a double-stranded helix, with the two strands connected by hydrogen bonds. Adenine pairs with Thymine, and Cytosine pairs with Guanine. 
  • Most DNA double helices are right-handed with ten nucleotides per turn, separated by a 3.4 Ã… translation along the helix axis.
  • Nucleotides are linked to each other by their phosphate groups, but this linkage runs in opposite directions on the different strands making the DNA double helix anti-parallel.
  • The outer edges of the nitrogen-containing bases are exposed.

 

Image showing the double helical structure of DNA and its complementary base pairing
Figure 3: (A) Simplified illustration of the double helical structure of DNA and its complementary base pairing. The sugar-phosphate backbone of the DNA molecule is shown as grey ribbons and the arrows running oppositely on the ribbons indicate that the two strands of DNA are anti-parallel. The four terminal bases are flattened instead of twisted to show the blown-up view of the hydrogen-bonded bases (image from Pray, L. 2008). (B) G.C and A.T Watson-Crick base pairing with the base atoms numbered in accordance with the standard nomenclature (image from Ghosh A, Bansal M. 2003).

 

Geometrical parameters and DNA structural conformations

The most recognized DNA form in living cells, and the one modelled by Watson and Crick, is widely known as B-DNA (Figure 3). However, depending on the DNA sequence and the environmental conditions in the biological systems, the geometries and dimensions of the double helix can vary; thereby leading to DNA structural polymorphism, which is important for its biological function (discussed in later section). These variations can be seen either in local structural parameters (Figure 4) or in the DNA handedness, base-pairing, or number of strands. The intrinsic flexibility of the polynucleotide backbone (including the puckering of the five-membered sugar ring) and rotation about the glycosyl bond (Figure 5) leads to the variations seen in DNA structures (Ghosh A, Bansal M. 2003). 

 

Schematic representation of DNA geometrical parameters
Figure 4: Schematic representation of DNA geometrical parameters (image from Olson et al., 2001.)

 

A ball-and-stick model showing the seven-backbone torsion angles in the repeating unit of a polynucleotide chain
Figure 5: A ball-and-stick model showing the seven-backbone torsion angles (details shown on left hand side) in the repeating unit of a polynucleotide chain. (Image created from PDB structure by Kiran Raj Takur, using UCSF Chimera).

 

There are two other commonly observed DNA conformations (Figure 6): (i) A-DNA, a right-handed helix that was first identified from X-ray diffraction studies on dehydrated DNA, and (ii) Z-DNA, a left-handed conformation. Due to the irregular and zig-zag shape of its backbone it is called Z-DNA. Table 1 compares the different helical parameters for A-, B- and Z-DNA.

 

Image displays three different conformations of DNA double helix: A-DNA, B-DNA and Z-DNA
Figure 6. Three different conformations of DNA double helix. (A) A-DNA, right-handed helix, from  . (B) B-DNA, right-handed helix, Watson and Crick model, from (C) Z-DNA, left-handed helix, from . The respective DNA sequences are given below. DNA backbone is tan colour with ribbon representation. Nucleotides A, T, G, Cs are shown in red, blue, green, and yellow respectively. (Image created by Kiran Raj Takur using UCSF Chimera).

 

Table showing geometric parameters of different forms of DNA
Table 1: Comparison of different helical parameters (average) for A-, B-, and Z-DNA (Ussery D.W., 2002).

 

Apart from the above described three popular DNA conformations, additional DNA polymorphs have been observed experimentally. It has become a common convention to associate a letter from the English alphabet to name the DNA structural polymorphs. All except the letters F, Q, U, V and Y are now known to be associated with a unique DNA form, illustrating the versatility of DNA structure (Ghosh A, Bansal M. 2003).

 

Biological relevance of Different types of DNA structures

The  large roll and tilt values of A-tracts (TATAAAA) enable rigid bending in B-DNA duplex upon binding of TATA Binding Protein and DNA transcription factor complex (TBP and DNA-TF complex, PDB ). This leads to local structural transition from B- to A-like conformation thereby making the DNA highly accessible for other transcription factors and RNA polymerase to initiate the gene expression. 

Alternating purine-pyrimidine dinucleotide repeat sequences (in the order GC>CA>TA) have the propensity to form Z-DNA. Z-DNA binding proteins like ADAR1 (Adenosine deaminase acting on RNA 1, PDB ) and DAI (DNA-dependent activator of IFN-regulatory factors, PDB ) act as immune regulators against foreign DNA, suggesting that Z-DNA plays a role in protection against infections. 

Thus, sequence dependent structural variations exhibit malleability in the local DNA structure which plays a significant role in protein recognition and binding.  

 

Did you know?

  • Not all human cells have a nucleus, the mature red blood cells in  humans do not have a nucleus and DNA. 
  • If all the DNA from a single human cell was stretched out end-to-end, it would make a six-foot-long strand. The sequenced human genome contains about 3 billion nucleotides. 
  • A rare Japanese canopy plant called Paris Japonica (Figure 7) has a genome size of roughly 150 billion nucleotides, making it 50 times the size of the human genome. It is the largest genome of any organism sequenced yet. 

 

Images of Paris Japonica. On the left a view of multiple flowers on a bush. On the right, a close up of the flower.
Figure 7: Paris Japonica, a rare Japanese flower (Image Source : wikipedia).

 

Vetriselvi Rangannan 

 

About the artwork:

The artwork for this article was created by Ruby, aged 16 years from the Leys School (Cambridge, UK). The DNA structure and its different forms inspired the artist to create a ‘wire shapingâ€� artwork illustrating the uniqueness of DNA to individuals, and to show its  responsibility for human traits. She used thread to represent the entanglement of DNA throughout human bodies to give physical structure with each colour representing how different components/strands of  DNA are held together to attain the double helical DNA structure.

View the artwork in the .

 

Structures mentioned in this article:

  1. Structure of a B-DNA dodecamer : Conformation and dynamics, PDB .
  2. GGGCATGCCC in the A-DNA Form PDB .
  3. Z-DNA dodecamer d(CGCGCGCGCGCG)2 at 0.75 A resolution solved by P-SAD. PDB .
  4. TFIIB (Human core domain)/TBP (A.Thaliana)/TATA Element ternary complex. PDB .
  5. Crystal structure of the ZALPHA Z-DNA complex. PDB .
  6. The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA. PDB . 

 

References:

  1. Ghosh A, Bansal M. (2003) Acta Crystallography D Biol Crystallography. D59:620-6.
  2. Olson, W. K., Bansal, M., Burley, S. K., Dickerson, R. E., Gerstein, M., Harvey, S. C., Heinemann, U., Lu, X. J., Neidle, S., Shakked, Z., Sklenar, H., Suzuki, M., Tung, C. S., Westhof, E., Wolberger, C. & Berman, H. M. (2001). J. Mol. Biol. 313, 229-237.
  3. Pray, L. (2008) Nature Education 1(1):100
  4. Ussery D.W. (2002). Encyclopedia of Life Sciences.