DNA or deoxyribonucleic acid, and is the carrier molecule of hereditary genetic information.
DNA is a very long molecule, made up of a succession of nucleotides added to each other by phosphodiester bonds. There are four different nucleotides: adenosine, cytidine, guanosine, and thymidine, whose sequence order is very precise and corresponds to genetic information.
The DNA macromolecule consists of two polynucleotide chains wound around each other in the form of a double helix. The chains are made up of links, or nucleotides, each comprising a sugar with five carbon atoms (deoxyribose), an organic base and a molecule of phosphoric acid.
There are four different organic bases (adenine, thymine, guanine and cytosine, designated by their initial: ATCG) which associate two by two according to a rigorously invariable order (thymine with adenine, guanine with cytosine), linking thus the two complementary chains by a loose chemical bond: a bridge of hydrogen atoms.
Such a structure ensures the cohesion of the double helix, but spares the possibility of separation of the two chains at the time of cell division (or mitosis).
He was a British physicist and Nobel Prize in Medicine. He developed the technique of visualization of the DNA molecule by X-ray diffraction in his London laboratory and played a decisive role in the development of the double helix theory.
It was in 1951, during a congress in Naples, that he presented the first DNA crystal shot that would give rise to his collaboration with Watson and Crick.
She was an English chemist and X-ray crystallographer. In London she devoted herself to the structure of DNA, where she worked with physicist Maurice Wilkins. Thanks to X-ray diffractometry, which she applies to DNA, Rosalind Franklin manages to determine its structure by distinguishing, thanks to her pictures, the two helices, named A and B.
James Watson and Francis Crick
On April 25, 1953, American geneticist James Watson and British physicist Francis Crick described the three-dimensional structure of DNA: a double helix wrapped around an axis. In 1962, Watson and Crick shared with Maurice Wilkins the Nobel Prize in Physiology and Medicine for their discovery.
The proper functioning of a cell is based on two classes of macromolecules: nucleic acids (DNA, repository of genetic information, and RNA, involved in the translation of this information) and proteins (products of the translation of information).
Proteins have various activities: catalysis (enzymes), storage of molecules (binding proteins), active or passive transport across membranes (transporters, channels), cellular communications (peptide hormones, receptors), architecture and movement (proteins of the cytoskeleton), recognition of non-self (antibodies)…
The relation with proteins…
The universal relationship between these macromolecules is expressed as follows: every protein is coded by a gene, a segment of DNA constituting a functional unit. The number of genes varies according to the organisms (about 2,500 in bacteria, 30,000 in the human species). The expression of a gene results in the synthesis of a specific protein.
In multicellular organisms, all the cells have the same stock of genes, inherited from a single initial cell (the egg resulting from fertilization), and yet they are not all identical, because they are capable of synthesizing more or less – if at all – the different proteins encoded in the genome, depending on their cell type and the developmental stage of the organism.
Thus, hemoglobin is produced in the precursors of red blood cells, antibodies in B lymphocytes, actin and myosin in muscle cells, keratin in those of the epidermis.
Moreover, certain proteins are produced only at the embryonic stage, the phenomena of development and differentiation relying on the differential expression of a common genetic material. Similarly, in adult organisms, the cell cycle involves the control of gene expression.
… And diseases
Many diseases, including cancers, viral infections, immune disorders and allergic reactions, as well as malformations during embryonic development, result from the excessive or insufficient production of certain proteins.
The control of gene expression is carried out at the level of DNA transcription by a family of proteins, the transcription regulators; these are encoded by regulatory genes, which could represent 5 to 10% of the total number of genes in higher eukaryotes.
It appears that many genetic disorders arise from mutations affecting regulatory genes.
The genetic code
Within genes, bases are organized into triplets called codons. The sequence of codons in DNA determines the sequence of amino acids that make up proteins, giving each protein its specificity. The genetic code is the linear and sequential reading code of DNA codons.
There are 20 natural amino acids, which are found in all living beings, from bacteria to humans.
Each protein is not synthesized directly from the image of the nucleotide sequence of DNA, but thanks to an intermediary: messenger RNA, whose structure is complementary to that of DNA, with this difference that thymine (T) is replaced there by uracil (U) – the four bases of RNA are therefore AUGC.
The process of synthesizing messenger RNA from chromosomal DNA is called transcription.
Thanks to the specificity of pairing between the bases, the information contained in the DNA is transmitted without any change to the RNA. This information is found in the nucleotide sequence, which determines the amino acid sequence.
Each amino acid in the protein chain corresponds to a sequence of three nucleotides in the chain, according to a relationship called the genetic code.
Given that each series of three nucleotides constitutes a codon and that four nucleotides by joining in threes give 64 possible combinations, in the hypothesis retained there would be 44 “excess” combinations, 44 types of triplets which would not correspond to any amino acid, since only 20 amino acids need to be synthesized.
In reality, we now know that all the triplets are used: some of them correspond to punctuation marks in the synthesis of a polypeptide chain, and moreover the code is in a way “degenerate”, i.e. to say that certain amino acids can be encoded by several different triplets.
DNA replication, which precedes any mitosis (cell division), as well as the first division of meiosis, allows a duplication of genetic information, so that it can be transmitted in its entirety to daughter cells.
DNA replication begins with the partial opening of the molecule and the separation of the two strands, and results in the formation of two long DNA molecules that are identical in all respects.
It is carried out according to a so-called semi-conservative model, in which each strand of the double helix generates a complementary strand then associates with it.
Replication is a very complex biochemical phenomenon requiring the participation of numerous enzymes whose role is to unwind the DNA filament, to separate the two strands, to synthesize the complementary strands and, finally, to reconstitute the native structure of the son strands.
DNA is a matrix from which all cells take the manufacturing plan for the different enzymes they need to function normally. It is therefore essential for their survival that the information contained in the double helix be reliable.
However, many substances or events are likely to alter its structure. Generally, this phenomenon is called mutation.
To overcome this drawback, there are normally enzymatic systems in all cells capable of detecting these alterations and repairing them. Their principle is relatively simple.
The abnormal fragment is excised by nucleases which degrade the DNA, then a DNA polymerase resynthesizes the correct fragment. Finally, a ligase ensures the covalent attachment of the newly formed strand.
DNA and discoveries around this subject contributed and continue to contribute to the evolution of methods in several disciplines.
For example, it is used in genetic engineering, scientific police, legal medicine, history and anthropology, bioinformatics, nanotechnologies and data storing and it is to be expected that new discoveries in the subject will continue to emerge and to find a practical application in several domains.