DNA Structure: 9 Important Factors Related To It

Contents

  • The chain of sugars connected by phosphodiester linkages is considered as the Nucleic acid backbone. 
  • Though the sugar-phosphate backbone is consistent in DNA and RNA, the nucleotide bases vary from one monomer to the next. 
  • The nucleotide bases are derived from purine guanine (G) and adenine (A), while the other two from pyrimidine uracil (U, RNA just) or thymine (T, DNA just) and cytosine (C).
  • The N-1 of a pyrimidine or N-9 of a purine is connected to C-1 of sugar.
  • A DNA strand also has terminals or ends similar to a polypeptide (carboxy and amino terminals). One end or terminal of the DNA strand has a free 5′ – Hydroxyl (or a 5′- hydroxyl group connected to a phosphate group). The opposite terminal or end has a 3 – Hydroxyl group. None of the ends is linked to another nucleotide. 
  • The nucleotide base pairing outcomes in arranging the DNA into a two-strand helical structure.
  • Erwin Chargaff proposed that the proportions of guanine to cytosine and of adenine to thymine were almost something similar in all species taken into consideration. 
  • The replication process is referred to as a semiconservative for DNA.
  • Simple stem-loop structure is observed when a nucleic acid has complementary sequences within the molecule and forms intra-molecular base pairing to form double-helical structures from a single nucleic acid molecule.

What is the structure of DNA

The pentose sugar deoxyribose is present in DNA structure (deoxyribonucleic acid). Its prefix deoxy demonstrates that the 2’ carbon atom of the deoxyribose sugar does not have the oxygen atom that is present with the 2’ carbon molecule of ribose sugar (the sugar in ribonucleic acid, or RNA), as displayed in the figure below. The pentose sugars in nucleic acids are bound to each other by phosphodiester linkages.

Figure: Structure of Ribose and Deoxyribose sugar found in RNA and DNA respectively https://commons.wikimedia.org/wiki/File:The_difference_between_ribose_and_deoxyribose.png

In particular, the 3’ hydroxyl (3 – OH) group of the ribose sugar of one nucleotide forms an ester bond with the phosphate, this phosphate group is also bonded to the 5’ OH group of the adjacent ribose sugar of the neighboring nucleotide. The chain of sugars connected by phosphodiester linkages is considered as the Nucleic acid backbone. 

Though the sugar-phosphate backbone is consistent in DNA and RNA, the nucleotide bases vary from one monomer to the next. 

Two of the nucleotide bases are derived from purine guanine (G) and adenine (A), while the other two from pyrimidine uracil (U, RNA just) or thymine (T, DNA just) and cytosine (C). To know more about nucleotides click here

Molecular structure of DNA

Primary structural Insights: The nucleic acids offer 3-D details on nucleotide base pairing, structure, and various other essential aspects of DNA and RNA. 

The smallest unit comprising of a base attached to a pentose sugar is alluded to as a nucleoside. The RNA contains four types of nucleoside units, namely:

cytidine, uridine, guanosine, and adenosine, while those in DNA are called deoxycytidine, deoxyguanosine, deoxyadenosine, and thymidine (Yes, Thymidine, you heard it right. Since it is not present in RNA, so no need to write deoxy as prefix). 

The N-1 of a pyrimidine or N-9 of a purine is connected to C-1 of sugar. The nitrogenous base is placed over the plane of pentose sugar when the design is viewed from a standard direction and orientation; this type of N-glycosidic linkage arrangement is referred to as β. 

A nucleotide is a nucleoside that is at least joined to one phosphate group through an ester linkage. The most widely recognized site of esterification and phosphate group attachment is usually the C-5 OH group of the pentose sugar. 

The nucleotide came into existence when a phosphate group binds to the C-5 of sugar present in the nucleoside. Thus, it is known as a 5 – nucleotide or a nucleoside 5 – phosphate. Say, for example, ATP is called adenosine 5 – triphosphate, and 3 – dGMP is known as deoxyguanosine 3 – monophosphate. 

This nucleotide is different from ATP in that it contains guanine instead of adenine. It contains deoxyribose instead of ribose (demonstrated by the prefix “d”). It includes one phosphate group instead of three. It has the phosphate esterified to the 3′ OH group instead of the 5′ position.

Nucleotides are monomers that connect among themselves to synthesize RNA and DNA. The nucleotide units found in DNA are of four types, namely:  

deoxycytidylate, deoxyguanylate, deoxyadenylate, and deoxythymidylate (or thymidylate). 

Important Note: Thymidylate contains deoxyribose. But, the prefix deoxy isn’t added because thymine nucleotides are not or are significantly less frequently found in RNA. 

The abbreviations like pACG or pApCpG signify a trinucleotide of DNA comprising deoxyadenylate monophosphate, deoxycytidylate monophosphate, and deoxyguanylate monophosphate connected by a phosphodiester bond, here “p” means a phosphate group. 

The 5′ end will usually have a phosphate linked to the 5 – Hydroxyl group. 

Important Note: A DNA strand also has terminals or ends similar to a polypeptide (carboxy and amino terminals). 

One end or terminal of the DNA strand has a free 5′ – Hydroxyl (or a 5′- hydroxyl group connected to a phosphate group). The opposite terminal or end has a 3 – Hydroxyl group. None of the ends is linked to another nucleotide. 

As a thumb rule, the nucleotide bases sequence of nucleic acid is written in the direction of 5′ to 3′. 

Therefore, the sequence ACG shows that the free 5’-hydroxyl group is present on deoxyadenylate, while the free 3;-Hydroxyl group is current on deoxyguanylate. Due to this polarity, ACG and GCA are considered as a different sets of sequences.

Who discovered the structure of DNA

The presence of complementary base pairing was found throughout studies coordinated for deciding the 3-D design of DNA. Rosalind Franklin and Maurice Wilkins got x-ray diffraction images of strands of DNA.

Figure: X-Ray diffraction image of DNA https://commons.wikimedia.org/wiki/File:ABDNAxrgpj.jpg#/media/File:ABDNAxrgpj.jpg

The attributes of these patterns of diffraction demonstrated that DNA was made of two chains that wrapped along with each other in a standard helical design. From this and additional relevant information, James Watson and Francis Crick constructed a primary model for DNA that represented the diffraction design and was additionally the source of some astounding insights of knowledge into the structural properties of DNA. 

DNA structure
Figure: Watson and Crick model of DNA structure
https://commons.wikimedia.org/wiki/File:DNA_scale_model.png

The highlights of the Watson-Crick model of DNA interpreted from the diffraction designs are: 

  1. The double-helical polynucleotide strands are looped around a single axis. The polynucleotide chains run in anti-parallel ways or opposite directions. 
  2. The backbone made up of sugar and phosphate is present at the external surface of the DNA, and, in this way, the purine and pyrimidine are placed inside the DNA double helix. 
  3. The nitrogenous bases are placed almost perpendicular to the helical axis, and the subsequent commands are separated by 3.4 Å. Thus, one turn of the spiral structure is completed after each 34 Å. Thus, ten bases per turn of a helix (34 Å per turn/3.4 Å per base). Hence a turn of 36 degrees per base (360 degrees for each total turn/10 bases for every turn) is experienced after every subsequent base incorporation. 
  4. 4. The distance between the two strands of DNA double helix is 20 Å.

DNA structure and replication

DNA and RNA are long (usually linear) polymers generally known as nucleic acids, which are responsible for transferring genetic (or hereditary) information to the offspring from parents. These bio-macromolecules comprise many connected nucleotides, each made of a pentose sugar, a phosphate group, and a nitrogenous base. The ribose sugars connected by phosphates groups form a typical and common backbone of DNA. The nitrogenous bases present in DNA are of Four basic types. The heritable genetic information is stored in a nucleotide sequence in the polynucleotide (nucleic acid) strand.

The bases have an extra exceptional property: they pair explicitly with each other that are stabilized and settled by non-covalent interactions like hydrogen bonds. 

The nucleotide base pairing outcomes in arranging the DNA into a two-strand helical structure. These nucleotide base pairs give way for replicating the hereditary (genetic) information present in the template nucleic acid strand to the newly synthesized nucleic acid strand. 

Figure: Schematic representation of DNA replication
https://commons.wikimedia.org/wiki/File:0323_DNA_Replication.jpg

Although RNA likely worked as the hereditary material significantly earlier, according to evolutionary history, the genes of many viruses and cells are composed of DNA. DNA polymerase is responsible for synthesizing (replicating) the DNA. These impeccably explicit enzymes duplicate nucleotide sequences from DNA templates with a mistake pace of under 1 out of 100 million nucleotide bases.

Double helix structure of DNA

The structure of nucleic acids represents their capacity to convey genetic information as an arrangement of nucleotide bases along a nucleic acid chain. Another property of nucleic acid is replication, that is the 

Synthesis of two duplicates of nucleic acid from a single copy using as a template. These characteristics depend on the types of nucleotide bases found in nucleic acids to form complementary base pairing for the synthesis of helical design comprising two strands. Thus, the DNA double helix structure promotes the replication of the hereditary material.

How is a remarkably regular construction ready to accommodate a self-assertive sequence of bases, given the various shapes and sizes of the pyrimidines and purines? In endeavoring to respond to this question, Watson and Crick found that guanine can be combined with cytosine, and adenine can pair with thymine to frame base pairing that has a similar shape. 

Figure: Pairing of nitrogenous bases in the DNA https://commons.wikimedia.org/wiki/File:DNA_chemical_structure.svg

These nucleotide base pairs are held together by non-covalent forces that are hydrogen bonds. This base-matching plan was upheld by earlier investigations of the base composition of DNA from various species. 

In 1950, Erwin Chargaff proposed that the proportions of guanine to cytosine and of adenine to thymine were almost something similar in all species taken into consideration. 

The importance of these equivalences was not apparent until the Watson-Crick model was given when it turned out to be clear that they address a fundamental aspect of DNA structure. 

The separation of roughly 3.4 Å between the following base pairs is much evident in the diffraction pattern of the double-helical DNA. 

The stacking of nucleotide bases provides additional stability to the DNA structure in a dual way.

In the first place, neighboring base pairs draw are attracted towards each other through van der Waals forces. However, Van der Waals forces are minimal, to such an extent that these associations contribute from 0.5 to 1.0 kcal per atom per mole. 

In the DNA double helix, in any case, countless atoms are in the influence of van der Waals forces, and the net impact added over these atoms is significant. Furthermore, the DNA double helix is also stabilized by the hydrophobic interactions resulting in the exposure of polar groups on the surface of the DNA double helix and hydrophobic groups in the structure’s interior. 

Base stacking in DNA is preferred by conforming to the rigid five-membered rings present in the sugar-phosphate backbone. The rigid nature of sugars influences both the single-stranded as well as double-stranded structures of DNA.

Structural differences between DNA and RNA

RNA, similar to DNA, is a long and unbranched polymer comprising nucleotides connected by 3’ 5’ phosphodiester linkages. 

The covalent design of RNA contrasts from that of DNA in two regards. As mentioned before and as shown by its name, the sugar sub-units in RNA are Ribose as opposed to deoxyriboses. Second, Ribose contains a 2’ OH group, which is not present in deoxyribose. 

Figure: Image to illustrate Structural Difference between DNA and RNA
https://commons.wikimedia.org/wiki/File:Difference_DNA_RNA-EN.svg

As a result, along with the standard 3’ 5’ phosphodiester linkage, another 2’ 5’ phosphodiester linkage is feasible for RNA. This 2’ 5’ phosphodiester linkage is significant in the expulsion of introns and the joining of exons for the arrangement of mature mRNA. 

The other contrast is that one of the four nucleotide bases found in RNA is uracil (U) rather than thymine (T). 

Important Note: Each phosphodiester linkage has a negative charge. This negative charge repulses nucleophilic species, for example, 

hydroxide ions; subsequently, phosphodiester linkages are considerably less reactive towards hydrolytic attack than the other esters like the esters of carboxylic acid. 

This obstruction is critical for keeping up the integrity of the genetic information stored in the nucleic acids. In addition, the 2’ – hydroxyl bunch in DNA further builds its protection from hydrolysis. 

The more superior stability of DNA presumably represents its utilization instead of RNA as the genetic material in every single cell and the majority of viruses.

A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar-Phosphate Backbone

The RNA and DNA are appropriate to work as the transporters of genetic information employing their covalent constructions. These macromolecules (polymers) are developed from end-to-end connections of their monomeric units. Every monomeric unit (nucleotide) inside the polymer (nucleic acid: DNA or RNA) comprises three fundamental components: a nitrogenous base, a pentose sugar, and a phosphate group. The arrangement of bases exceptionally portrays a nucleic acid and addresses a linear form of genetic information.

The genes translate the type of proteins that are required by cells. However, DNA isn’t the immediate template for the synthesis of protein. 

The immediate template for the synthesis of protein is RNA (ribonucleic acid). Specifically, a class of RNA, known as the messenger RNA (mRNA), acts as an information carrier to synthesize proteins. Other RNAs, such as ribosomal RNA (rRNA) and transfer RNA (tRNA), also play an essential role in protein synthesis. RNA polymerases synthesize all types of cellular RNA for taking instructions from DNA templates. The mRNA is produced in response to transcription events, while this mRNA acts as a template for translation, which eventually results in the formation of proteins.

This progression of genetic information is solely dependent upon the genetic code, which characterizes the connection between the nucleotide bases sequence in DNA (or in transcribed mRNA) and the amino acids sequence in a protein. 

The genetic code is almost identical in the whole life forms: a grouping of three bases, called a codon, determines an amino acid. Codons in mRNA are perused consecutively by tRNA molecules, which act as an adapter molecule during the synthesis of protein on ribosomes. 

The ribosomes are the complex associations of rRNAs and about 50 other types of proteins. 

The last subject to be considered is the interrupted property of most genes found in eukaryotes; they exhibit exons and introns, which act as mosaics of nucleic acid sequences. Both exons and introns are transcribed through DNA. However, introns are removed from mature mRNA molecules. Thus, the presence of introns and exons has critical importance in protein evolution.

Genetic information carrying capacity of DNA

A striking attribute of a DNA strand or fragment is its length. A DNA strand should involve numerous nucleotides to convey the genetic information vital for the organism. For instance, the DNA of 

polyomavirus, which can cause malignancy in several microorganisms, its DNA is up to 5100 nucleotides long. 

We can calculate the genetic information conveying the capacity of nucleic acids in an accompanying manner. 

Each position in a DNA double helix is a pair of nucleotide bases, relating it to two bits of information (22 = 4). 

if, a nucleic acid chain has 5100 nucleotides, it relates to 2 × 5100 = 10,200 bits of information 

or 1275 bytes of information as (1 byte = 8 bits)

The genome of E. coli is a DNA molecule in the form of a single circular chromosomal. It comprises two chains of 4.6 million nucleotides which relate to 9.2 million bits, or 1.15 megabytes, of data. 

DNA in higher vertebrates are a lot bigger molecules. For example, the human genome includes around 3 billion nucleotides, split between 24 chromosomes [22 autosomes, x and y allosomes (sex chromosomes)] of various sizes. 

One of the most significant known DNA molecules is an Asiatic deer (the Indian muntjak). Its genome is as extensive as the human genome yet is present in just three chromosomes. 

The biggest of these chromosomes has more than 1 billion nucleotides. If such a DNA particle could be expanded entirely, it would extend more than 1 foot in length. A few plants also contain considerably bigger DNA particles.

Transmission of genetic information

The DNA double-helical structure and the presence of nucleotide base pairs illustrate the process of replication of the genetic material. The nucleotide base sequence of one strand of the DNA double helix decides the nucleotide base sequence of the other strand; the base pairing of the complementary strand takes place following Chargaff’s rule. In this way, 

Segregation of the strands of DNA double helix acts as a template for synthesizing two new strands. These newly formed strands have the same sequence as that of the parent DNA because both the strands undergo replication.

Subsequently, as DNA is synthesized (replicated), one of the chains of every daughter DNA would be from the parent DNA, and another chain is newly synthesized. A semiconservative DNA replication mechanism accomplishes this dissemination of parental DNA strands. 

Franklin Stahl and Matthew Meselson did an introductory trial of this theory in 1958. First, they tagged the parent DNA with 15N, a heavier isotope of nitrogen, so that the synthesized DNA becomes denser than normal DNA. Next, the labeled DNA was produced by E. coli, growing in a medium containing 15NH4Cl as the only nitrogen source. After the replication step utilizing the heavier nitrogen was finished, the E. coli cells were then moved to a medium that contained 14N, the standard isotope of nitrogen. 

A general question in every mind right now is: What is the dissemination of 14N and 15N in the DNA particles after subsequent replication cycles? 

The arrangement of 14N and 15N was uncovered by the strategy of density gradient centrifugation or sedimentation. First, a small quantity of DNA was solubilized in a concentrated cesium chloride solution of density(1.7 g cm 3) close to the thickness of DNA. 

This solution was later centrifuged and equilibrated. The equilibration and diffusion formed a gradient of cesium chloride concentration in the centrifuge tube, which resulted in the formation of a density gradient (1.66 – 1.76 g cm3).

The DNA fragments move (under the influence of centrifugal force) according to their respective densities in the centrifuge tube containing cesium chloride density gradient.

The DNA accumulated and formed a narrow band that was identified by its intrinsic property of absorbing ultraviolet light. The hybrid of 14N DNA and 15N DNA strands showed a discrete band since it has a density between the 14N duplex and 15 N duplex. 

DNA was obtained from the E. coli cells at different times after moving from a 15N to a 14N containing growth medium and then centrifuged. 

Investigation of DNA samples showed that a single band of hybrid DNA was observed after one generation. The band was found somewhere between the 14N DNA and 15N DNA densities bands. The absence of the 15N DNA band reflects that parental DNA was not conserved totally during the replication. 

Furthermore, the absence of a 14N DNA band suggests that all the daughter DNA is comprised of a strand of 15N DNA. This ratio should be half because the density of the DNA hybrid band was somewhere between the densities of the 14N DNA and 15N DNA. 

After two divisions in bacteria, there were an equivalent amount of DNA bands. One was the band of DNA hybrid, and the second band was 14N DNA. Stahl and Meselson interpreted from these investigations “that equal division of nitrogen in the DNA molecule takes place and each daughter molecule receives one DNA strand with 14 N and other with 15N. Thus, the replication process is referred to as a semiconservative for DNA.

Meselson and Stahl’s experiment results are following the DNA replication model proposed by Watson and Crick.

Figure: Experimental design of Meselson and Stahl’s experiment
https://commons.wikimedia.org/wiki/File:OSC_Microbio_11_02_MesStahl.jpg

Tertiary structure of DNA

Some DNA Molecules Are Circular and Supercoiled

The DNA in human chromosomes is linear in structure. However, studies like electron microscopy revealed that circular DNA molecules are also found in some organisms. 

Important Note: The word circular is used to mention the continuity of the DNA molecule, not for its morphological appearance.

The DNA molecule present in the cellular environment is usually found in a minimal and compact shape.

Note:  A fully stretched chromosome of E. coli is around 1000 times its diameter. 

Another unique characteristic came into light when the DNA transforms into a circular form from linear. The helical axis twists to produce a super-helix. 

A circular DNA molecule with no superhelical turns is referred to as a relaxed circular DNA molecule. 

Supercoiling is a biological phenomenon that happens because of the following two reasons:

– The supercoiled DNA is way more compact than relaxed DNA. 

– Second, supercoiling regulates the unwinding and interaction capabilities of the DNA double helix.

Structural analysis of single stranded DNA

Single-stranded molecules of nucleic acids usually exhibit intra-molecular overlapping to adopt different structures. Thus, during evolution, nucleic acids adapted various structures and conformations for their transmission and stored the genetic information, especially the RNA molecules. 

These confirmations and structures are also essential for higher organisms, such as ribosomes, which are a complex association of RNA and proteins and play a crucial role in synthesizing proteins. 

It is frequently observed that a simple stem-loop structure is observed when a nucleic acid has complementary sequences within the molecule and forms intra-molecular base pairing to form double-helical structures from a single nucleic acid molecule.

Generally, these double-helical structures are made following the Watson-Crick base pairing pattern. However, these structures also contain some unmatched bases (appear as a bulged region) and mismatched base pairs.

This mismatching affects the functioning and higher-order folding of DNA double helix by inducing deviations from the standard structure and destabilizing the local structure of nucleic acids.

Single-strand nucleic acids can attain much more complex structures than the stem-loops by interacting with the bases located far from each other. For this purpose, at least three bases may associate with the stabilization of these structures. 

Figure: Stem-Loop structure generally found in nucleic acids
https://commons.wikimedia.org/wiki/File:Stem-loop.svg

In such cases, hydrogen bond acceptors and donors that generally take part in Watson-Crick base pairing may also participate in hydrogen bonding in non-standard base pairs. In addition, ions of strong metals such as magnesium (Mg2+) are actively involved in stabilizing these structures.

Conclusions

in this article we have discussed about the DNA structure in details to gain better insights into the composition and structure of DNA and RNA. To know more about the higher order structure click here

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