10.2: Introduction

Deoxyribonucleic acid (DNA)

DNA is the hereditary molecule in all cells. The double helix structure of DNA has a backbone consisting of a five-carbon sugar (deoxyribose) and phosphate groups connected by phosphodiester linkages. Attached to the backbone are four nitrogen bases. The sequence of the four bases is the genetic code, the hereditary information of the cell. The bases of one strand of the double helix are hydrogen bonded to the bases of the other strand in a complementary manner. The base thymine (T) is always hydrogen bonded to adenine (A); cytosine (C) is always hydrogen bonded to guanine (G).

Nucleoside vs. Nucleotide

A nucleoside is the combination of a sugar with a nitrogen base. A sugar, a nitrogen base, and a phosphate group combine to form a nucleotide. DNA and RNA are polymers of nucleotides in which the sugars are deoxyribose and ribose, respectively.

Replication

When a cell divides, each daughter cell receives DNA identical to the parent cell through the process of replication. During replication of DNA, the double helical structure of DNA unwinds and each strand serves as the template for the synthesis of a new complementary strand of DNA.

Transcription of DNA to RNA

Each cell must synthesize protein and each protein must have a specific order of amino acids (the primary structure of the protein). The sequence of nitrogen bases in DNA contains the genetic information required to assemble the amino acids in the correct order. Another nucleic acid called the ribonucleic acid (RNA), copies the genetic information from DNA and uses that information to direct the synthesis of protein in the cell’s ribosomes. Like DNA, RNA has a backbone made of a five-carbon sugar with ester linkages to phosphate groups; however, the sugar in RNA is ribose rather than deoxyribose. Four nitrogen bases are attached to the backbone; three of the bases (adenine, cytosine and guanine) are the same as in DNA. The RNA base uracil replaces the DNA base thymine. Several types of RNA exist, usually with a single-strand of nucleic acid.

The preliminary step in protein synthesis is a transcription of the genetic information from a segment of DNA to messenger RNA (mRNA). This step is similar to the replication of DNA but only a segment of the DNA chain is copied, not the entire chain. During transcription the nitrogen bases of DNA hydrogen bond to the nitrogen bases of mRNA. Cytosine (C) is hydrogen bonded only to guanine (G) and adenine (A) is always hydrogen bonded to uracil (U) or thymine (T).

Translation of mRNA (Protein synthesis)

The genetic information is transcribed from DNA to mRNA in the nucleus of the cell. After being synthesized, the mRNA migrates to the cell’s ribosomes.

Another form of RNA, called the transfer RNA (tRNA) is much smaller than other nucleic acids. Each tRNA molecule is specifically designed for a particular amino acid. The amino acid becomes attached to the end of its tRNA molecule. One after another, tRNA molecules hydrogen bond to mRNA; the amino acids carried by the tRNA are assembled in sequence to make a protein. The order of the amino acid assembly is determined by the sequence of nitrogen bases in the mRNA. A sequence of three nitrogen bases on mRNA is a codon. The nitrogen bases of the mRNA codon, hydrogen bond to complementary nitrogen bases in the anticodon of the tRNA. Most of the 20 common amino acids have more than one codon. For example, UUU and UUC are both codons for the amino acid phenylalanine.

Summary

Transcription copies genetic information from DNA to RNA. The actual synthesis of the protein occurs during translation when the sequence of nitrogen bases is translated into the sequence of amino acids of the protein. The key to the translation is matching of specific amino acids to the codons of the mRNA using complementary anticodons on tRNA.

Reverse transcription “Why medications are not available to completely cure certain diseases”.

Some viruses called retroviruses do not contain DNA. One such example is the HIV (the virus that transmits (AIDS) which is a RNA containing virus. This virus reproduces by taking over the host cell’s machinery to produce new DNA that carries the information for the manufacture of viral nucleic acids and proteins. Therefore, the viruses thrive. Influenza, mumps and polio are other examples of RNA viruses. The enzyme involved in the reverse transcription is called reverse transcriptase. It is not as efficient as the DNA polymerase and so the virus rapidly mutates into new forms.

How does one control the AIDS virus?

The anti-AIDS drug zidovudine (AZT) has been around for a while and is a competitive inhibitor of an enzyme involved in the production of the HIV virus in the reverse transcription process. After being administered, AZT is converted to AZT triphosphate which closely resembles in structure one of the enzyme substrates dTTP responsible for the production of viral DNA from the viral RNA. The growing DNA chain now having incorporated an AZT triphosphate is unable to complete the synthesis of the DNA.

Mutation, genetic disease and the malaria connection

Any permanent change in the primary structure of the DNA is called mutation. Errors in replication, exposure to mutagens which include X-rays, UV radiation, nuclear radiation and chemicals are common causes of mutations. While some mutations have no effect on an individual or their off-spring, if these mutations take place in the egg or sperm cells it can be inherited and are called genetic diseases. There are over 4000 identified genetic diseases in humans. Some populations have higher rates of genetic anomalies.  Sickle cell anemia is one such genetic disorder and results from a single amino acid change in a hemoglobin molecule.  This disease is most prevalent among people with ancestors that were originally from lands that are close to the equator where there are lots of mosquitoes.  It is thought that a mild form of the disease protects people from malaria infection.

The woman behind the scenes

Rosalind Franklin made crucial contribution to the discovery of DNA although her name did not appear in the Nobel Prize awarded for this achievement. Her X-ray diffraction pictures of DNA were used by James Watson, Francis Crick and Maurice Wilkins as they correctly predicted the structure of DNA.  Rosalind was working on the possible structure of DNA and even suggested the double helix structure but she did not publish her hunches, she was a very meticulous scientist and was doing very thorough analyses of her x-ray crystallography data.  Even though they were working in the same lab, at King's College in the University of London, personality differences precluded Franklin and Wilkins from being collaborators.  Thus, Wilkins showed her data to Watson and Crick (without her consent or knowledge) and this allowed them to complete the puzzle utilizing 3-D molecular models.

The Nobel Prize went to Watson, Crick and Wilkins for the discovery of how DNA encodes information that is passed from one generation to the next.  This prize was awarded in 1962, four years after Franklin died from ovarian cancer.  The Nobel Prize is not awarded posthumously, and it is awarded to no more than three scientists.  Thus, there is some controversy over whether she would have shared the prize if she had lived long enough^§.  

^§Reference:
McGrayne, Sharon Bertsch, Nobel Prize Women in Science, Carol Publishing Group, New York, 1993 pp 304-332.

This exercise was modified from the following experiment without the use of the model kit recommended:

Experiment # 24: DNA and RNA; Laboratory Experiments; Chemistry and the living organism; 6^th edition by Bloomfield and Stephens.