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Tuesday, 23 April 2013

DNA structure

DNA structure – An overview
The DNA structure consists of two chainlike molecules (polynucleotides) that twist around each other to form the classic double-helix. The cell’s machinery forms polynucleotide chains by linking together four nucleotides. The nucleotides which are used to build DNA chains are adenosine (A), guanosine (G), cytidine (C), and thymidine (T). DNA houses the information required to make all the polypeptides used by the cell. The sequence of nucleotides in DNA strands (called a ‘gene’) specifies the sequence of amino acids in polypeptide chains.

Clearly a one-to-one relationship cannot exist between the four nucleotides of the DNA structure and the twenty amino acids used to assemble polypeptides. The cell therefore uses groupings of three nucleotides (called ‘codons’) to specify twenty different amino acids. Each codon specifies an amino acid.

Because some codons are redundant, the amino acid sequence for a given polypeptide chain can be specified by several different nucleotide sequences. In fact, research has confirmed that the cell does not randomly make use of redundant codons to specify a particular amino acid in a polypeptide chain. Rather, there appears to be a delicate rationale behind codon usage in genes.

DNA structure – Fine-tuning and optimization
Highly repetitive nucleotide sequences lack stability and mutate readily. However, a study involving the genomes of different organisms at the University of California suggests that codon usage in genes is actually designed to avoid the type of repetition that leads to unstable sequences! Further research indicates that codon usage in genes is also set up to maximize the accuracy of protein synthesis at the ribosome.

Furthermore, the components which comprise the nucleotides also appear to have been carefully chosen in view of enhanced performance. Nucleotides that form the strands of the DNA structure are complex molecules which consist of both a phosphate moiety and a nucleobase (adenine, guanine, cytosine or thymine) joined to a five-carbon sugar (deoxyribose). In RNA, the five-carbon sugar ribose replaces deoxyribose.

The phosphate group of one nucleotide links to the deoxyribose unit of another to form the backbone of the DNA strand. The nucleobases form the ‘ladder rungs’ when the two strands align and twist to form the classical double-helix structure.

Scientists have long known that a myriad of sugars and numerous other nucleobases could have conceivably become part of the cell’s information storage medium (DNA). But why do the nucleotide subunits of DNA and RNA consist of those particular components? Phosphates can form bonds with two sugars simultaneously (called phosphodiester bonds) to bridge two nucleotides, while retaining a negative charge. This makes this chemical group perfectly suited to form a stable backbone for the DNA molecule. Other compounds can form bonds between two sugars but are not able to retain a negative charge. The negative charge on the phosphate group imparts the DNA backbone with stability, thus giving it protection from cleavage by reactive water molecules. Furthermore, the intrinsic nature of the phosphodiester bonds is also finely-tuned. For instance, the phophodiester linkage that bridges the ribose sugar of RNA could involve the 5’ OH of one ribose molecule with either the 2’ OH or 3’ OH of the adjacent ribose molecule. RNA exclusively makes use of 5’ to 3’ bonding. As it turns out, the 5’ to 3’ linkages impart far greater stability to the RNA molecule than does the 5’ to 2’ bonds.

Why do deoxyribose and ribose serve as the backbone constituents of DNA and RNA respectively? Both are five-carbon sugars which form five-membered rings. It is possible to make DNA analogues using a wide range of different sugars that contain four, five and six carbons that can form five- and six-membered rings. But these DNA variants possess undesirable properties as compared to DNA and RNA. For instance, some DNA analogues do not form double helices. Others do, but the nucleotide strands either interact too tightly or too weakly, or they display inappropriate selectivity in their associations. Furthermore, DNA analogues made from sugars that form 6-membered rings adopt too many structural conformations. In this event, it becomes exceptionally difficult for the cell’s machinery to properly execute DNA replication and transcription. Other research shows that deoxyribose uniquely provides the necessary space within the backbone region of the double helix of DNA to accommodate the large nucleobases. No other sugar fulfils this requirement.
DNA structure – Conclusion
The molecular constituents of the DNA structure appear to have optimized chemical properties to produce a stable helical structure capable of storing the information required for the cell’s operation. Detailed accounts of how such an optimized structure for the cell’s most fundamental information storage medium could have arisen naturally have not been produced. To suppose that such extensive optimization could have come into being by blind chance is a far greater leap of faith than many would be willing to take.