DNA

The nucleotides of DNA join in the following structural configuration:

- - -  hydrogen bond

H
\
H N N -- H - - - - O CH₂
\ // \ / \\ /
C C -- C C -- C
\ // \\ / \
N -- C N - - - - H -- N C -- H
\ / \ /
N == C C -- N
adenine \ / thymine
H O

H
/
H N O - - - - - H -- N H
\ // \ // \ /
C C -- C C -- C
\ // \ // \\
N -- C N -- H - - - - - N C -- H
\ / \ /
N == C C -- N
\ //
guanine N -- H - - - - - O cytosine
/
H

Beginning in the nucleus, the DNA molecule of the eukaryotic cell will be transcribed. The enzyme RNA polymerase separates the two strands of DNA and attaches the complementary nucleotides. The section of DNA being transcribed is the transcription unit. The RNA grows in a 5' to 3' direction. The initiation site for RNA synthesis is bound to by RNA polymerases. The promoter is the initiation site, and nucleotide sequences that RNA polymerase need transcription factors (specific proteins) to recognize. After the enzyme reaches the segment that is a termination signal, it stops adding nucleotides. This primary transcript is then processed to be functional mRNA. The ends are modified to protect, lengthen, and help the strand be recognized. A 5' cap of guanine and a Poly (A) cap (added to the 3' end) of adenine are attached. This messengerRNA now leaves the cell to give the message from the DNA to make polypeptides.

Translation occurs with the transferRNA (tRNA). It goes to the aminoacyl-tRNA synthetase, which joins an amino acid to its specific tRNA. The initiation is where mRNA, the tRNA with the first amino acid, and the two subunits of a ribosome come together. The mRNA molecule is in triplets known as codons. The tRNA matches up complementary triplets of anticodons. Elongation occurs with codon recognition where hydrogen bonds form with the mRNA codon and the tRNA anticodon. Then a peptide bond forms so that the new polypeptide is added to the growing chain. Translocation occurs so that the tRNA goes to the exit site and then leaves. Once the tRNA codes for the terminating (or stop) codon, elongation stops. The chain of amino acids then goes where it needs to (e.g. with others, an organelle, etc.)

A deletion or addition in DNA nucleotides would throw off the reading frame. Wrong triplets will be formed, and the wrong amino acids will be coded for. This would form an incorrect polypeptide chain and mess things up. A substitution in one of the nucleotides might not be as bad. It would only mess up its particular triplet. Even then, wobble may allow the tRNA to still code for the correct amino acid and there wouldn't be a problem.

P.S. Yes, this is all me...

Now, for something completely different in this node -- this time somewhat more useless. Next is a Python script to calculate a DNA sequence for any stream given in standard input.

#!/usr/bin/python
import sys
g = ('a','c','g','t')
gencode=lambda x:[ sys.stdout.write("%s%s%s%s "%(g[int(ord(y))/64],\
                   g[(int(ord(y))%64)/16],\
                   g[((int(ord(y))%64)%16)/4],\
                   g[((int(ord(y))%64)%16)%4]))\
                   for y in tuple(x)]

if __name__ == "__main__":
  while 1: 
   try: gencode(raw_input())
   except: break 
  print

Example session:

$ ./dna.py < dna.py

agat agac agtt ctcc ctat ctag agtt cgag cggc cgtg agtt ctaa

ctgc ctca cgga cgtt cgtg cggc cgtc ctaa cgtt ctag ctca agaa

ctat ctgc ctat cgct agaa attc agaa agga ...

The discovery of the structure of DNA

In 1943 american scientist Oswald Avery proved that DNA, and not proteins, as had been previously thought, carried the genetic information of a cell, resulting in several attempts to discover the structure of DNA. By the 1950s, a number of dicoveries about DNA had been made, but the full structure was yet to be found. Two main teams were working on it in England: Maurice Wilkins, and Rosalind Franklin were attempting to deduce the structure through X-ray spectroscopy at King's college London, while James Watson and Francis Crick were working on a more theoretical basis, by trying to work out what structures could have the necessary properties for DNA at Cambridge. While Watson and Crick took the credit for the structure of DNA, it is known that much of their work was based on X-ray data shown to them by Maurice Wilkins, and taken by Rosalind Franklin. The data showed the helical structure that is distinctive of DNA. Franklin's role in the discovery of DNA was crucial, and she never received much of the credit for it as she died shortly afterwards of cancer.

Structure of DNA

DNA is a polynucleotide ie. it is composed of many base units called nucleotides. Each DNA nucleotide is composed of a phosphate group, a deoxyribose sugar, and a nitrogenous base (one of thymine, guanine, adenine, and cytosine). The phosphate group and the deoxyribose sugar form an alternating chain, often called the sugar-phosphate backbone, of the DNA molecule, while the nitrogenous bases "stick out" to one side. In the double helix structure, hydrogen bonds form between thymine and adenine and cytosine and guanine, bonding the two chains together.

§

DNA is short for deoxyribonucelic acid and is usually referred to as a "blueprint" for the creation of biological structures found in living organisms. Most DNA is found in the nucleus of cells within an organism, although some DNA is stored in the mitrochondria, also. DNA contains inherited information which is coded into it by using combinations of four different chemical bases which are: adenine (A), guanine (G), thymine (T), and cytosine (C). These chemical bases are attached to a phosphate-deoxyribose "backbone," and the bases form weak hydrogen bonds with each other in A—T G—C pairs, creating two interlocked strands that are often referred to as a "double-helix" or a "ladder."

§

A------T
C--------G
G--------C
A-------T
A----T
G
C--G
T-----A
A--------T
G---------C
A--------T
G-----C
T
A--T
T------A
C--------G
T--------A

§

The Chemical Structure of DNA

The chemical bases, adenine, thymine, guanine and cytosine have slightly varying chemical compositions. All four are made up of oxygen, carbon, nitrogen and hydrogen, and all four attach to a phosphate molecule and a deoxyribose molecule, and this combination creates what is called a nucleotide. Each individual nucleotide, i.e., each chemical base-phosphate-deoxyribose combination is linked in a certain order which will determine the makeup of the gene or the organism.

• Purines: The chemical bases adenine and guanine are called purines. Purines are organic compounds that are made of a pyrimidine ring and a imidazole ring that are both nitrogenous.
  • Adenine: 6-amino purine
  • Guanine: 2-amino-6-oxy purine
• Pyrimidines: The chemical bases thymine and cytocine are called pyrimidines. Pyrimidines are organic compounds that consist of a nitrogenous pyrimidine ring.
• Thymine: 2,4-dioxy-5-methyl pyrimidine
• Cytosine: 2-oxy-4-amino pyrimidine

Due to the two rings that make up purines, they are significantly larger in size than pyrimidines. The size difference is why only adenine-thymine and guanine-cytosine pairs can exist; if any other pairs tried to form, they would be either too large or too small to fit into the DNA polymer. This pairing is called complementary base pairing.

The Biological Functions of DNA

DNA functions inside the cells of organisms by forming specific sequences of nucleotides that form genes. Higher order plants and animals can have many thousands of genes that exist on chromosomes. In such cells, the DNA molecules are coiled around proteins called histones, which are also formed into chromosomes. These are located inside of the nucleus of the cell, which has two copies of them, and when a cell reproduces, all of these chromosomes are coped and distributed to the reproduced cells. This process is called mitosis. In meiosis, however, reproduction instead involves sex cells which each only carry one copy of each chromosome, but the fertilized cell created by them will carry two copies of each chromosome.

DNA replication is the process by which genetic information can be copied and passed on to other cells. Due to the nature of the double-sided strands that make up DNA molecules, it can reproduce by splitting itself down the center. Each side can act as a "template" for the creation of its partner side, since only one pairing is possible with the chemical base that remains. This process of "unzipping" a DNA double-helix is called semiconservative replication. A junction is created by the enzyme gyrase called the replication fork which forms where the hydrogen bonds that hold the chemical bases together break apart through the action of the enzyme helicase. The new molecule is created by the enzyme polymerase which synthesizes new nucleotides to add to the unzipped strands. The specific mechanisms of this process will vary depending upon whether an organism is prokaryotic or eukaryotic.

When DNA is defined as containing and carrying genetic information, what we are really saying is that DNA is coded with information on making the proteins which will make up the physical structures within an organism. Depending on the order of the nucleotides within the DNA molecule, amino acids will by synthesized in a certain way to form these proteins. The amino acids are identified within the code depending on the sequence of the bases. From the four bases, codons are created which are like words that name which of the twenty amino acids should be used in the making of the protein. A group of three nucleotides will create one codon. It can take up to 1,000 codons, or 3,000 nucleotides, to mark the specifications of a given protein.

Mutations and Variations of DNA

There are various things which can happen which can alter or damage the sequence of DNA, which may have the possible effect of altering the formation of proteins. These cases include:

1. Environmental Damage: Exposure to agents like ultraviolet light, nuclear radiation, or chemicals can alter DNA in several ways. Generally, an agent will cause damage to the chemical bases of the nucleotide, altering its structure so that upon replication, it may mistakenly be copied onto a wrong base. Damage can also be called to the deoxyribose-phosphate backbone of the DNA. Broken segments of DNA will sometimes try to connect with other ends of DNA within a cell, causing what is known as a translocation mutation.



2. Errors in Replication: During the process of semiconservative replication, the enzyme polymerase will sometimes synthesize a chemical base incorrectly, causing an error at that side that can effect the gene. However, these mistakes are usually corrected very quickly by special proteins within the cell that indentify and fix such errors. Since there is a large amount of redundancies within the code, effects may not be noticed at all. If the error does occur in a part of the code that creates an important protein, a genetic disease may result.



3. DNA Fragmentation: Within the chromosome, pieces of DNA can sometimes break apart or fall off, creating fragments that may be integrated into a different section of the molecule. When this happens, it can be difficult for the cell to repair it. This can activate mutant forms of the gene or supress genes that are involved in the control of tumor growth, which can lead to cancer.

Applications

• Forensic Science:

Analysis of DNA found at crime scenes has become a critical part of building cases in criminal investigations. The reason for this is that by isolating sections of an individual's DNA that differentiate it from others human beings can positively identify an individual and link them to a crime scene. One one tenth of one percent of a person's DNA makes it distinctive from others'. These specific DNA markers are isolated and looked at for elimination purposes.

RELATED NODES: CODIS, Canadian DNA Database, Genetic Sequence Comparisons, DNA Sequencing

• Genetic Engineering:

By isolating sections of DNA for analysis, genetic engineering seeks to modify or manipulate an organism's genes in order to introduce more favorable characteristics to it. The results of this research have been various, with the technology being used in pharmaceutical development and perhaps better known in the creation of genetically modified organisms. Those are types of produce that have been altered through genetic engineering to resist pests, stay fresh longer, and have longer growing seasons.

RELATED NODES: Retroactive genetic engineering, Glossary of Genetics terms, quantitative genetics, plasmid DNA isolation

Discovering DNA: History & Research

DNA was first isolated in 1869 by Friedrich Miescher, a Swiss scientist. He named the acidic compound that he found within the cells he was studying nuclein. It took another 70 years for scientists to fully analyze the components of the molecule and to identify the chemical bases of adenine, thymine, guanine and cytosine. In 1943, Oswald Avery found through his work that DNA was responsible for carrying inheritable genetic information. However, it was in 1953 when American chemist Linus Pauling first claimed to have discovered the structure of the molecule. His unpublished paper was reviewed by two other scientists: James Watson, and American scientist, and Francis Crick, a Brtish scientist. They knew that his findings were inaccurate due to their own advances in research, and sought to publish a paper that would correctly detail the structure of DNA.

On March 7, 1953, Watson and Crick finished construction on a six foot long model of the molecule, which correctly had the chemical bases bonded to each other attached to the sugar-phosphate backbones. Their paper was published in Nature on April 25, 1953. After several years of research, their work had been thoroughly verified and accepted by the general scientific community. They received the Nobel Prize for Physiology or Medicine in 1962 for their research. They received the prize along with Maurice Wilkins, a researcher who had published a paper on DNA crystallography at the same time. Rosalind Franklin, who worked with Wilkins at Kings College in London on this research, died in 1958 before the prize was awarded.

---

Sources
http://www.genome.gov/25520880
http://library.med.utah.edu/NetBiochem/pupyr/pp.htm
http://www.accessexcellence.org/AE/AEC/CC/DNA_structure.html
http://online.sfsu.edu/~rone/GEessays/gedanger.htm
Altmann, H.. ed. DNA Repair Mechanisms. Schattuer & Stuttgart. 1972.
Guschlbauer, W.. Nucleic Acid Structure: An Introduction. Springer-Verlag. 1976.
Lagerkvist, U. DNA Pioneers and Their Legacy. Yale University Press. 1998.