Strung Through All The Cells- The DNA

Invention & History of DNA

Long before the recorded work of DNA discovery, In 1866 Gregor Mendel known as the father of genetics suggested his Mendelian principles which stated that characteristics of each organism are passed from generation to generation. He coined the most familiar terms, dominant and recessive.

Later in 1869, Friedrich Miescher identified a substance from the molecule isolated from a pus cell nucleus which he obtained from the waste deposit of a clinical hospital. He termed it “nuclein” as he found it in the nucleus of the cell. He obtained these from lymphocytes present in the bandage he obtained.

In 1881, German biochemist Albrecht Kossel identified nuclein as a nucleic acid-containing five nitrogen bases as its building blocks, namely Adenine, Cytosine, Guanine, and Thymine. In 1882, Walther Flemming discovered mitosis and proved the passage of genetic characteristics while the cell divides in its embryonic stage through DNA.

Erwin Chargaff highlighted this concept and took it forward for research and came up with Chargaff rules of inheritance. After multiple kinds of research by various scientists on this topic, In 1953 Watson and Crick came up with the double-helical structure of this nucleic acid called DNA. This was the innovative finding which led to the development of genetics to a level we have today. Often Friederich Miescher is forgotten among these numerous Nobel prize winners who worked on DNA.

Structure & Features of DNA

This macro molecule consists of two strands that twist around a common axis in a shape called the double helix. The double helix looks like a twisted ladder and its rungs are composed of pairs of nitrogenous bases that hold them together.

Each strand of DNA is a polynucleotide, composed of units called nucleotides made of three components, a sugar molecule, a phosphate group, and a nitrogenous base. The sugar molecule present is called deoxyribose hence the name DNA whereas the nucleic acid RNA has ribose sugar.

Sugars of one nucleotide are joined to the phosphate group of the next nucleotide using covalent bonds. This forms the sugar-phosphate backbone. Four nitrogenous bases occur in DNA molecules, namely; adenine, cytosine, guanine, and thymine (abbreviated as A, C, G, and T respectively). 

The sequence of nitrogenous bases on one strand of DNA molecule complementary matches with the other strand of DNA molecule. This is referred to as complementary pairing or bases are complementary to each other and is denoted as prime (‘). For example x’-y’ is read as x prime- y prime.

Hence the base pairs are read as 5`-3` and 3`-5`. This complementary pairing is since adenine and guanine are purine compounds but cytosine and thymine are pyrimidine compounds. Both possess different chemical structures.

Each strand of DNA denotes a particular code for synthesizing proteins. Certain sequences of these bases encode particular RNA molecules and these sequences are referred to as genes. These genes help in transcribing mRNA and translating it into useful proteins. Chromosomes vary widely in their number of base pairs and genes.

The longest chromosome in human cells, chromosome 1 is around 249 million base pairs long and has between 2000- 2100 distinct genes. However, genes make up only 1% of DNA in humans. Few genes that do not code are separated by sequences of nitrogenous bases that don’t provide instructions for RNA synthesis. This region is called the intergenic region and the non-coding DNA is called introns.

Introns are important as they provide binding sites for proteins that activate or deactivate the process of transcription and they provide protection for exons which are the coding regions of DNA. Human DNA is unique, even though it is made up of nearly 3 billion base pairs, about 99 percent of them are the same in every human. 

Working of The DNA

DNA works by copying itself into a single-stranded molecule called RNA. If DNA is the blueprint, then RNA is the translator of instructions written in the blueprint. During this process, DNA unwinds itself so it can be replicated. RNA acts as a messenger, carrying vital genetic information in a cell from DNA through ribosomes to create proteins, which then form all living things.

In humans and most of the eukaryotes, the process of protein synthesis using DNA and RNA takes place as two sets and it always takes place in the nucleus of the cells at the site of these nucleic acids.

1. Transcription

Transcription is the first part of the central dogma of molecular biology, that is the change of DNA to RNA. It is the transfer of genetic instructions in DNA to mRNA. During transcription, a strand of mRNA is made to complement a strand of DNA. It takes place in three steps; Initiation is the beginning of transcription.

It occurs when the enzyme RNA polymerase binds to a region of a gene called the promoter. This signals the DNA to unwind so the enzyme can “read” the bases in one of the DNA strands. The enzyme is ready to make a strand of mRNA with a complementary sequence of bases. Elongation is the addition of nucleotides to the mRNA strand and Termination is the ending of transcription. The mRNA strand is complete, and it detaches from DNA.

In eukaryotes, the new mRNA is not yet ready for translation. At this stage, it is called pre-mRNA, and it must go through more processing before it leaves the nucleus as mature mRNA. The process again undergoes three steps i.e., Splicing, Editing and Polyadenylation.

Splicing removes introns from mRNA, the remaining mRNA consists only of regions called exons that code for the protein. The ribonucleoproteins are small proteins in the nucleus that contain RNA and are needed for the splicing process. Editing changes some of the nucleotides in mRNA. For example, a human protein called APOB, which helps transport lipids in the blood, has two different forms because of editing. One form is smaller than the other because editing adds an earlier stop signal in mRNA. Polyadenylation adds a “tail” to the mRNA. The tail consists of a string of As (adenine bases). It signals the end of mRNA. It is also involved in exporting mRNA from the nucleus, and it protects mRNA from enzymes that might break it down.

2. Translation

It is the process in which the genetic code in mRNA (messenger RNA) is read to make a protein. After mRNA leaves the nucleus, it moves to a ribosome, which consists of rRNA (ribosomal RNA) and proteins. The ribosome reads the sequence of codons in mRNA, and molecules of tRNA(transfer RNA) bring amino acids to the ribosome in the correct sequence.

Each tRNA molecule has an anticodon for the amino acid it carries. An anticodon is complementary to the codon for an amino acid. Wherever the codon AAG appears in mRNA, a UUC anticodon of tRNA temporarily binds. While bound to mRNA, tRNA gives up its amino acid. With the help of rRNA, bonds form between the amino acids as they are brought one by one to the ribosome, creating a polypeptide chain. The chain of amino acids keeps growing until a stop codon is reached.

After a polypeptide chain is synthesized, it may undergo additional processes. For example, it may assume a folded shape due to interactions between its amino acids. It may also bind with other polypeptides or with different types of molecules, such as lipids or carbohydrates. Many proteins travel to the Golgi apparatus within the cytoplasm to be modified.

Future That DNA Holds

This complex structure holds within one of the largest science revolutions it could probably make. Its complexity still provides researchers with enough inventions to keep pondering about. DNA insights are already enabling the diagnosis and treatment of genetic diseases.

Science is also hopeful that medicine will advance to be able to leverage the power of our cells to fight disease. Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology.