Molecular Biology: The Genetic Code

At the heart of molecular biology lies the notion of “information”. This information is transferred from the language of 4 letters of DNA (A,T,C,G) to the language of 20 amino acids in the proteins. The genetic code is a set of rules by which this flow of information happens. To be more specific, the code maps tri-nucleotide sequences with a single amino acid i.e. a specific sequence of 3 consecutive bases in DNA code for a particular amino acid. There are 4 bases in DNA thus the possible combinations of 3 consecutive bases (by permutation) is 43 i.e. 64. These triplet combinations are called codons. Out of the 64 possible codons, 61 encode for one of the 20 amino acids used for protein synthesis.

To bring this concept in the picture of the central dogma, it should be understood that DNA acts as a template for the synthesis of a complementary messenger RNA (mRNA) which is transported to the cytoplasm. At the cytoplasm, it is used by the ribosomes to produce protein. The ribosome decodes the mRNA and start polymerizing amino acids, the sequence of which is determined by the triplet codon in the mRNA.

Thus, the sequence of bases in the DNA determines the sequence of amino acids in the newly synthesized polypeptide chain. This sequence of amino acids determines the final structure of the protein which in turn determines its biological function.

Further Reading

  1. Web address   http://www.youtube.com/watch?v=q6PP-C4udkA
  2. Web address   http://www.youtube.com/watch?v=yqESR7E4b_8
  3. Web address   http://www.youtube.com/watch?v=YxLdBNAxqKg

Replication: How does DNA multiply?

Molecular Biology Series Continued

Cells need to divide continuously by a process called cell division. When new cells are formed from existing cells, the DNA also needs to be multiplied so that the new cells may get their share. DNA replication is a process by which DNA makes copies of itself. After understanding the complementary nature of the two strands in a DNA, it should be straight forward to imagine that each of these strands serve as a template for the synthesis of a new complementary daughter strand. For DNA to replicate, the two strands need to separate. After the separation, each strand functions as a template for the synthesis of a new strand, this happens due to the complementary nature of the bases. A free (unpolymerized) nucleotide recognizes its complementary nucleotide in the template and forms the hydrogen bond, at the same time; it aligns itself for enzyme-catalyzed polymerization into a new DNA chain. The polymerization is carried out by an enzyme called DNA-polymerase which forms the phosphodiester bond between the sugar of the free nucleotide and the phosphate group of the already existing one. DNA replication is an important process which ensures the proper distribution of genetic material into each cell during cell division and also facilitates the formation of numerous copies of a certain gene when required.

 

Mechanism of DNA replication: Each strand of the parent DNA serves as a template for the new strand.

 

 

Semiconservative nature of DNA replication: Each of the daughters of the dividing cells inherit a new combination of DNA double helix i.e. one old and one new strand.

 

Molecular Biology Series: Proteins and Amino Acids

Structurally, proteins are polymers of amino acids. Amino acids are carbon compounds consisting of two side chains: basic amine (NH2) and acidic carboxylic acid (COOH) groups. The variable R-group is what gives amino acid its distinctive characteristic i.e. amino acids differ only due to the R-group. There are 20 different types of amino acids which makeup all the proteins in the body. An amino acid joins with another amino acid through a peptide bond i.e. a bond between carboxylic group of one and amine group of the next amino acid. Thus a polymer of amino acid is formed called polypeptide. Longer polypeptides eventually fold and a structural protein is formed.

The content and precise sequence of amino acids in a protein is encoded by the precise sequence of bases in the DNA. This precise sequence of amino acids is then responsible to determine the biological function of the protein. The sequence of amino acids also determines how the protein folds to make a 3D structure which is a prerequisite for its biological function. For e.g. many enzymes catalyze certain chemical reactions by binding with the substrate molecule. This binding is only possible when protein folds into a precise 3D structure which makes it possible for it to bind to the substrate in the precisely needed fashion. Just a little mistake and the precise binding does not possible thus the reaction fails to proceed. The field of protein folding, structure and stability has been one of the most important research fields for many years and still remain one of the unsolved mysteries.

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Structure of amino acids: Every amino acid consists of a basic amino and an acidic carboxyl group connected to a central Carbon molecule. The R-group attached to the central Carbon is what gives individual amino acid its identity.

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A polypeptide chain: Peptide bond between adjacent amino acids i.e. between carboxyl group from one and amine group from the other amino acid forms a polypeptide.

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Folding of a polynucleotide chain: A polypeptide chain of more than 100 amino acids can fold into a protein which has precise 3D structure and is biologically active


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Central Dogma of Molecular Biology (Series)

DNA is found inside the nucleus in the chromosomes whereas the site of protein synthesis is outside the nucleus in the cytoplasm. Thus, direct production of protein from the DNA sequence is not possible. Exceptions exist, for example prions or prion-like proteins. The lack of exist of cellular machinery that can synthesize proteins directly from DNA maybe also due to the fact that RNA evolved before DNA. In fact, convincing evidences can be found which suggest that DNA is result of evolution of RNA to store the information in a safer manner i.e. for survival. In any case, central dogma of molecular biology is the backbone of molecular biology upon which today’s science exists. It shows the flow of information from DNA to protein. First postulated by Francis Crick (co-receiver of Noble prize in physiology and medicine for discovering the structure of DNA), the central dogma states that sequence of bases in DNA determine the sequence of bases in RNA (which is also a polymer of ribose nucleotide different from DNA) by a process called transcription, this sequence of RNA polymer then determine the sequence of amino acids in a protein. Protein is a polymer of amino acids.  There have been many modifications to the central dogma. For e.g. reverse transcription i.e. formation of DNA from RNA has been found and so on. However, the basic principle is still among the most widely seen phenomenon.

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Central Dogma: DNA can duplicate (replication), make RNA (transcription), this RNA is transported to the cytoplasm where it is used by the cellular machinery for translation (synthesis of protein)


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Molecular Biology Series: The Structure of DNA

Being a deoxyribose nucleic acid, a strand of DNA is made up of by the repetition of nucleotides each of which consists of a deoxyribose sugar, attached to one of the four nucleic acid bases (adenine, guanine, cytosine and uracil). Each sugar-base combination is joined with each other by a phosphodiester linkage between the sugar molecules thus forming a polynucleotide.

DNA is a double helical molecule; there are two strands running in anti-parallel direction i.e. opposite in polarity. These two strands are held together by weak hydrogen bonds between the bases.

This pairing between the bases is made possible by the specific structure and meticulous precision of the specificity of possible pairing between the 4 bases. Adenine can pair only with thymine but not with other bases and vice versa. Similarly, cytosine can pair with guanine and not any other bases and vice versa. This means that the number of adenine must be equal to the number of thymine and the number of cytosine must be equal to the number of guanine in a stretch of DNA. This is often called Chargaff’s rule named after its discoverer.

Since DNA is a polymer of deoxyribose nucleotide the sequence of the bases which appear in a certain stretch of DNA determines the information it codes for. Human genome consists of about 3 billion bases. Not all DNA in the chromosome encode for a protein, some DNA sequences encode a protein (called genes), others encode only RNAs but those never form proteins. These two are called structural DNA. Other DNA sequences either function as regulatory DNA to regulate the production of RNA and/or protein or are vestige of evolution. Surprisingly, structural DNA sequences make up less than 2% of the human genome. Most of it consists of what was previously considered to be “junk DNA” i.e. DNA stretches without function. Today it is known that “junk DNA” is not junk after all. Everyday scientists are discovering specific roles for these non-structural DNA elements especially related to regulation of production of RNA/proteins. Thus the “information” about an organism or its “blue print” is encoded in the DNA but for that information to manifest as a visible trait or phenotype either as physical appearance, behavior or mental state, that information needs to transfer into proteins. After an enormous complexity of regulation and interaction with the environment, protein is formed and it gets involved in its specific function. At an instant of time, enormous amounts of genes continuously produce proteins which continuously perform their functions to keep a cell alive. A group of working cells make tissues, group of tissues make organs and a proper combination of functional organs make up an organism.

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Schematic diagram showing the base pairing: Due to the structure of the bases adenine can only base pair with thymine and cytosine can base pair only with guanine. This hydrogen-bond is what holds the two strands of DNA together.

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Structure of a nucleotide: The sugar (deoxyribose) pairs with one of the bases to form a nucleotide.

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Structure of a polynucleotide: Adjacent nucleotides join to form a DNA strand. Nucleotides connect through a phosphodiester bond between phosphate group (P) of one nucleotide and the deoxyribose sugar (D) of another.

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Double helical structure of a DNA: Two strands of DNA (polynucleotides: colored red and blue) are helically coiled around each other and held together by weak hydrogen bonds between the bases of each nucleotide.

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