Title Med-RM_Bot_SP-3_Ch-15_Molecular Basis of Inheritance.pdf ✅

Chapter Contents Aakash Educational Services Limited - Regd. Office : Aakash Tower, 8, Pusa Road, New Delhi-110005 Ph. 011-47623456 The DNA The Search for Genetic Material RNA World Replication Transcription Genetic Code Translation Regulation of Gene Expression Human Genome Project DNA Fingerprinting “Factors/Genes” were first detected and analyzed by Mendel and subsequently many other scientists, by following their patterns of transmission from generation to generation. Later investigations confirmed that DNA acts as genetic material in all living organisms. However, viruses have either DNA or RNA as their genetic material. THE DNA DNA is a long polymer of deoxyribonucleotides. It is an acidic substance present in nucleus, which was first identified by Friedrich Meischer in 1869. He named it as “Nuclein”. Altmann found these substances to be acidic in nature, hence he named it nucleic acid. The length of DNA is usually defined as number of nucleotides or a pair of nucleotide referred to as base pairs (bp) present in it. This also is the characteristic of an organism. Few examples are given below : Organism Genetic material No. of nucleotides or bp 174 bacteriophage ssDNA, Circular 5386 bases Lambda () phage  dsDNA, Linear 48502 bp Escherichia coli dsDNA, Circular 4.6 × 10 bp 6 Human genome dsDNA, Linear 3.3 × 10 bp 9 Structure of Polynucleotide Chain The basic unit of DNA is a nucleotide which has three components – a nitrogenous base, a pentose sugar (deoxyribose) and a phosphate group. There are two types of nitrogenous bases : (i) Purines : Heterocyclic, 9-membered double-ring structure with N at position 1, 3, 7 and 9, e.g., Adenine (A) and Guanine (G). (ii) Pyrimidines : Heterocyclic, 6-membered single-ring structure with N at 1 and 3 position, e.g., Cytosine (C), Thymine and Uracil. Cytosine is common in both DNA and RNA; thymine is present in DNA and uracil is present in RNA at the place of thymine. Chapter 15 Molecular Basis of Inheritance
130 Molecular Basis of Inheritance NEET Aakash Educational Services Limited - Regd. Office : Aakash Tower, 8, Pusa Road, New Delhi-110005 Ph. 011-47623456 A polynucleotide chain shows following types of linkage or bond in its components : (i) N-glycosidic linkage : A nitrogenous base is linked to the pentose sugar through a N-glycosidic linkage to form a nucleoside. Purine nucleosides have 1 — 9 glycosidic linkage (carbon 1of sugar and 9 position of A/G). Pyrimidine nucleosides have 1 — 1 linkage i.e., sugar carbon 1 and 1 position of T/C). (ii) Phosphoester linkage : When a phosphate group is linked to 5 – OH of a nucleoside through phosphoester linkage a corresponding nucleotide is formed. Two nucleotides are linked through 3— 5 phosphodiester linkage to form a dinucleotide. A polymer thus formed has a free phosphate moiety at 5-end of sugar, which is referred as 5-end of polynucleotide chain. Similarly, at the other end of the polymer the sugar has a free 3-OH group which is referred to as 3-end of polynucleotide chain. The backbone in a polynucleotide chain is formed due to sugar and phosphates. The nitrogenous base linked to sugar moiety projects from the backbone. 5 phosphate  3 hydroxyl  Fig. : A Polynucleotide chain Types of Nucleosides in DNA Types of Nucleotides in DNA (i) Deoxyadenosine (A + S) P = dAMP (deox + yadenosine monophosphate) (ii) Deoxyguanosine (G + S) P = dGMP (deoxyguanosine monophosphate) (iii) Deoxycytidine (C + S) P = dCMP (deoxycytidine monophosphate) (iv) Deoxythymidine (T + S) P = dTMP (deoxythymidine monophosphate) Types of Nucleosides in RNA Types of Nucleotides in RNA (i) Adenosine (A + S) P = AMP (adenosine monophosphate) (ii) Guanosine (G + S) P = GMP (Guanosine monophosphate) (iii) Cytidine (C + S) P = CMP (Cytidine monophosphate) (iv) Uridine (U + S) P = UMP (Uridine ) monophosphate + + + + + + + Note : S and P represents sugar and phosphate respectively. Sugar is ribose (C5H10O5) in RNA and deoxyribose (C5H10O4) in DNA. Derivation of DNA Structure Two lines of investigations helped in derivation of DNA structure i.e., X-ray Crystallography and Chargaff’s rule. (a) X-ray Crystallography : Maurice Wilkins and Rosalind Franklin obtained very fine X-ray diffraction pictures of DNA. It was suggested that structure of DNA was sort of helix with 3.4 Å periodicity. But they had not proposed a definitive model for DNA. (b) Erwin Chargaff’s Rules : Chargaff’s along with his colleagues, performed base composition studies and put forward certain generalisations for double-stranded DNA, called as Chargaff’s rule (Not applicable for single-stranded DNA). (i) Purines and pyrimidines occur in equal amounts. (ii) Purines found in DNA are adenine and guanine. Pyrimidines of DNA are thymine and cytosine. A + G = T + C
NEET Molecular Basis of Inheritance 131 Aakash Educational Services Limited - Regd. Office : Aakash Tower, 8, Pusa Road, New Delhi-110005 Ph. 011-47623456 (iii) A G 1 T C    , this value is constant for all species. (iv) Base ratio A T C G   is specific for a species. It is used to identify the species. It is less than one in prokaryotes, e.g., E. coli = 0.92 and more than one in eukaryotes, e.g., Humans = 1.52. (v) Sugar deoxyribose and phosphate residues occur in equal number. (vi) Purine adenine is equimolar with pyrimidine thymine. (vii) Purine guanine is equimolar with pyrimidine cytosine. James Watson and Francis Crick on the basis of previous informations proposed a very simple but famous double helix model for the structure of DNA. One of the hallmarks of their proposition was base pairing between the two strands of polynucleotide chains. However this proposition was based on the observations of Erwin Chargaff. 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 other strand can be predicted. Thus if one DNA strand has A, the other would have T and if one has G, the other would have C. Therefore, if the base sequence of one strand is CATTAGGAC, the base sequence of other strand would be GTAATCCTG. Also, if each strand from a DNA acts as template for synthesis of a new strand, the two double-stranded DNA or daughter DNA produced would be identical to the parental DNA molecule. Salient features of the double helix structure of DNA are : (i) DNA consists of two polynucleotide chains. The backbone is constituted by sugar-phosphate and the bases project inside. (ii) The two chains of DNA run in anti-parallel fashion with 5  3 polarity in one and 3  5 polarity in other chain. CATTAGGACTCA GTAA T CC TGAGT 5 3 3 5 (iii) The bases in two strands are paired through hydrogen bonds forming base pairs (bp). Adenine forms two H-bonds with thymine from opposite strand and viceversa. Similarly, guanine is bonded with cytosine with three H-bonds. As a result, always a purine comes opposite to a pyrimidine. This generates approximately uniform distance between the two strands of helix. Glycosidic bond Phosphodiester bond hydrogen bonds Double-stranded polynucleotide chain
132 Molecular Basis of Inheritance NEET Aakash Educational Services Limited - Regd. Office : Aakash Tower, 8, Pusa Road, New Delhi-110005 Ph. 011-47623456 Strand 1 Strand 2 Shallow Groove 3.4 Å Deep Groove Phosphate Deoxyribose sugar G C T A A T C G 34 Å Hydrogen bonds A T Strand 1 Strand 2 T A G C C G A T C G G C Deoxyribose Phosphate Purines A Adenine G Guanine Pyrimidines T Thymine C Cytosine Nucleotide The DNA double helix Diagrammatic representation of the DNA molecule Helix length 5 P 3 OH  5 P 3 OH  (iv) The double chain of DNA is helically twisted in a right-handed fashion. (v) Each turn of double helix or the pitch of the helix is 3.4 nm (a nanometer is one billionth of a meter, that is 10–9 m). It has roughly 10 base pairs in each turn. The distance between two adjacent base pairs is approximately equal to 0.34 nm. (vi) The plane of one base pair stacks over the other in double helix. This, in addition to H-bonds, confers stability to the helical structure. Note : (i) Types of DNA and their comparison. DNA types Base pairs per turn ( ) n Rotation Vertical rise per bp Helical diameter bp ( ) h A B C Z 11 10 9.33 12 Right handed Right handed Right handed Left handed 2.56 Å 20 Å 19 Å 18.4 Å 23 Å 3.4 Å 3.3 Å 3.8 Å (ii) Linear double-stranded DNA in eukaryotes and PPLO (Monerans)