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Class 12 molecular basis of inheritance DNA Vs RNA

GENETIC MATERIAL (DNA Versus RNA)

A molecule that can act as a genetic material should replicate, chemically and structurally be stable, undergo mutation, and able to express itself in the form of “Mendelian Characters”.

l      So far the rules of base pairing and complementarity, both DNA and RNA have the ability to direct their duplications, but proteins fail.  The two strands of DNA being complementary if separated by heating come together when appropriate conditions are provided.  Further, 2’-OH group present in pentose sugar of every nucleotide in RNA is a reactive group that makes RNA liable and easily degradable.  RNA is also now known to be catalytic, hence reactive.  Therefore, DNA chemically is less reactive and structurally more stable when compared to RNA.  Therefore, among the two nucleic acids, DNA is a better genetic material.

l      The presence of thymine at the place of uracil also confers additional stability to DNA.  Both DNA and RNA are able to mutate.  In fact, RNA being unstable mutates at a faster rate.  Consequently, viruses having RNA genome and have a shorter life span mutate and evolve faster.

l      RNA can directly code for the synthesis of proteins, hence can easily express the characters.  DNA, however, is dependent on RNA for synthesis of proteins.  protein-synthesizing machinery has evolved around RNA.  Thus, both RNA and DNA can function as genetic material, but DNA being more stable is preferred for storage of genetic information.  However, for the transmission of genetic information, RNA is better.

RNA WORLD

l      The phrase, “RNA World” was first used by Nobel laureate Walter Gibert in 1986.  The RNA World hypothesis proposes a  world filled with RNA based life.  RNA, which can store information like DNA and catalyze reactions like proteins (enzymes), may have supported cellular or pre-cellular life.

l      RNA was the first genetic material. There is now enough evidence to suggest that essential life processes (such as metabolism, translation, splicing, etc) evolved around RNA.  RNA used to act as a genetic material as well as a catalyst (there are some important biochemical reactions in living systems that are catalysed by RNA catalyst, not by protein enzymes).  However, RNA being a catalyst was reactive and hence unstable. Therefore, DNA has evolved from RNA with chemical modifications that make it more stable.  DNA is double-stranded and having complementary strands further resists changes by evolving a process of repair.

NUCLEIC ACIDS

l      Nucleic acids are highly complex organic acids, present in all living cells.

l      Nucleic acid is so-called because it occurs primarily in the nucleus and has acidic nature.

l      Nucleic acid was first isolated in 1869 by a Swiss physician Friedrich Miescher from the nuclei of pus cells.  He called it nuclein.  Zacharias (1881) found nuclein to be restricted to chromatin.  Fisher  (1880) discovered purine and pyrimidine bases.  Oskar Hertwig (1884) considered nuclein to be the substance responsible for the transmission of hereditary characters.  Nuclein was renamed nucleic acids.  Levene (1910) found phosphoric acid as the constituent of nucleic acid.  Behrens (1938) showed that most of the DNA is in the nucleus and most of RNA is in the cytoplasm.  Erwin Chargaff (1950) showed that DNA contains equal proportions of purines and pyrimidines.  Shapiro (1969)  obtained the first photograph of Lac gene.

STRUCTURE OF DNA

l      In prokaryotic cells, DNA occurs in the cytoplasm and is the only component of the prochromosomes and plasmids.  In eukaryotic cells, DNA is largely confined to the nucleus and is the main component of chromosomes.   It is called nuclear  DNA.  It is combined with proteins, forming deoxyribonucleoprotein (DNP).  A small quantity of  DNA also occurs in the mitochondria and plastids.  This is called extranuclear or organellar DNA.  It is not associated with proteins like the prokaryotic DNA.

l      DNA is the polymer of several thousand pairs of nucleotide monomers (W.T. Astbury, 1940).  The length of DNA is usually defined as the number of nucleotide pair (base pairs) present in it.  This also is the characteristic of an organism.  A bacteriophage fx174 has 5386 nucleotides, lambda phage has 48502 base pairs, E. coli has 4.6x106base pairs and haploid content of human has 3.3x109  base pairs.  Each nucleotide consists of a pentose sugar, a nitrogenous base and inorganic phosphate.  A combination of a base with pentose sugar is called nucleoside.

       Ä    Nucleoside = Pentose sugar + Nitrogenous base

       Ä    Nucleotide = Pentose sugar + Nitrogenous base + Inorganic phosphate

l Chemical structure of DNA was explained by P.A. Levene.  DNA is the largest biomolecule, also the largest macromolecule.

PENTOSE SUGAR

l      It is a carbohydrate-containing 5-carbon atom.  Out of 5-carbons, 4-carbons and one oxygen form a 5-membered ring.  The fifth carbon is out of the ring and forms part of the group.

l The pentose sugar in a nucleic acid can be either deoxyribose (in DNA) or of ribose type (in RNA).  The position of the -OH group is at C-atoms 1’, 3’ and 5’ in deoxyribose sugar.  But in ribose sugar, the position of -OH group is at 1’, 2’, 3’, and 5’ C-atoms.  The missing oxygen at the position in the deoxyribose sugar explains the prefix 2— “deoxy”.

NITROGENOUS BASES

l      The nitrogenous bases are of two main types, pyrimidines and purines.

PYRAMIDINES

l      The pyrimidines are single benzene ring compounds in which carbon atoms 1’ and 3’ are replaced by N-atoms.

l      There are three most common pyrimidines- Thymine (T), Cytosine (C) and Uracil (C).

l      Thymine is found in DNA and uracil is present in RNA.

PURINES

l      There are two main purine bases, (A) and guanine (G).  The purines are 9-membered double-ring compound, i.e., consisting of a 5 membered imidazole ring joined to a 6-membered pyrimidine ring at positions 4’ and 5’.

l      The positions of N-atom are at 1’, 3’, 7’ and 9’.  The two most common purines are Adenine (A) and Guanine (G).

INORGANIC PHOSPHATE

l      It is present in the form of phosphoric acid, which esterifies the – of pentose sugar and makes the genetic material acidic in nature.

l      It combines with pentose sugar molecules at 5th and 3rd carbon of sugar by a phosphodiester linkage.

l      The two chains of DNA molecules run in opposite directions.  This means that the carbon atom at position 5’ in the sugar component is in one direction in one chain and is in the opposite direction in the other chain.  Thus, the two chains are parallel directions of the two chains of DNA molecule provide the basis for the precise replication of DNA and proper transcription of RNA.

MODEL OF DNA

l      J.D. Watson and F.H.C. Crick (1953) postulated a precise, three-dimensional right-handed double-helical model of DNA on the basis of X-ray crystallography done by M.H.F. Wilkins.

l      X-ray diffraction of DNA by W.T. Astbury (1940s) showed that the DNA is a polynucleotide, and occurs at intervals of 3.4 A°.

l      In 1962 Watson, Crick and Wilkins were awarded Nobel  Prize for this work

l      The DNA molecule consists of two helically twisted, antiparallel polydeoxyribonucleotide by ‘steps’.  The polynucleotide strands which form the backbone of DNA molecules are constituted by alternate sugar-phosphate.

l      In the genetic discussion, one strand of the double helix is conveniently referred to as Watson (W), the other strands as Crick (C).

l      Each step is made up of a double ring purine base and a single ring pyrimidine base.  The purine and pyrimidine bases are connected to deoxyribose sugar, directed inside the helix and are stacked on top of each other like a pile of saucers.

l      The nitrogenous bases of two strands are linked through H-bonds.  H-bonds are the only attractive force between the two strands and serve to hold the structure together.  In addition to H-bonds, sickness of the plane of base pairs confers the stability of the helical structure.

l      The two strands in a double helix are complementary, intertwined in a clockwise direction (right-handed helix) around a common axis like a rope staircase and run in the opposite direction (antiparallel).

l      The coiling produces alternate major and minor grooves. The major groove is about 22 A° wide and the minor groove is about 12 A° wide.  The minor groove is the distance between the paired molecules while the major groove is the space between successive turns when the pair is wound into a helix.

l     One turn of the spiral has a distance of 34A° and has 10 base pairs (bp) so that the spacing between adjacent base pairs is 3.4A°.  Each successive nucleotide turns 36° in the horizontal plane.  The helix is 20A° in diameter.

BASE PAIRING

l      The purine and pyrimidine bases pair only in certain combinations.  Adenine (A) pairs with thymine (T) and guanine (G) with cytosine (C).  The total width of the pair is 10.7A°.

l        Adenine and thymine are joined by two H-bonds (A=T) through atoms attached to positions 6’ and 1’.  Cytosine and guanine are joined by 3 H-bonds through atoms attached to positions 6’, 1’ and 2’.  Thus, there are only four possible base pairs: A=T, T=A, GC, and CG, in DNA.

l      The base pairing confers a very unique property to the polynucleotide chains.  They are said to be complementary to each other, and therefore, if the sequence of bases in one strand is known then the sequence in another strand can be predicted.  Also, if each strand from a DNA (say parental DNA) acts as a template for synthesis of a new strand, the two double-stranded DNA (daughter DNA) thus, DNA molecule.  Because of this, the genetic implications of the structure of DNA became very clear.

l      The pyrimidines and purines are linked to the deoxyribose sugar by glycosidic bonds.  The linkage in pyrimidine nucleosides is between position 1’ of deoxyribose and 3’ of pyrimidine.  In purine nucleosides, the linkage is between position 1’ of deoxyribose and 9’ of the purine.

l      Each phosphate group is joined to a carbon atom 3’ of one deoxyribose and a carbon atom 5’ of another by a phosphodiester bond.  Thus, each strand has a 3’ end and 5’ end.  Thus, the oxygen atoms of deoxyribose point in opposite directions in the two strands.

l      These 3’-5’ phosphodiester bonds provide considerable stiffness to the polynucleotide. Both glycosidic and phosphodiester bonds are formed by condensation reactions that involve the elimination of water.

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