Molecular Basis of Inheritance PDF

CHAPTER 5 MOLECULAR BASIS OF INHERITANCE 5.1 The DNA 5.2 The Search for Genetic Material In the previous chapter, you have learnt the inheritance patterns and the genetic basis of such patterns. At the 5.3 RNA World time of...

CHAPTER 5 MOLECULAR BASIS OF INHERITANCE 5.1 The DNA 5.2 The Search for Genetic Material In the previous chapter, you have learnt the inheritance patterns and the genetic basis of such patterns. At the 5.3 RNA World time of Mendel, the nature of those ‘factors’ regulating 5.4 Replication the pattern of inheritance was not clear. Over the next hundred years, the nature of the putative genetic material 5.5 Transcription was investigated culminating in the realisation that 5.6 Genetic Code DNA – deoxyribonucleic acid – is the genetic material, at least for the majority of organisms. In class XI you have 5.7 Translation learnt that nucleic acids are polymers of nucleotides. 5.8 Regulation of Gene Deoxyribonucleic acid (DNA) and ribonucleic acid Expression (RNA) are the two types of nucleic acids found in living 5.9 Human Genome Project systems. DNA acts as the genetic material in most of the organisms. RNA though it also acts as a genetic material 5.10 DNA Fingerprinting in some viruses, mostly functions as a messenger. RNA has additional roles as well. It functions as adapter, structural, and in some cases as a catalytic molecule. In Class XI you have already learnt the structures of nucleotides and the way these monomer units are linked to form nucleic acid polymers. In this chapter we are going to discuss the structure of DNA, its replication, the process of making RNA from DNA (transcription), the genetic code that determines the sequences of amino acids in proteins, the process of protein synthesis (translation) and elementary basis of their regulation. The determination 2024-25  BIOLOGY of complete nucleotide sequence of human genome during last decade has set in a new era of genomics. In the last section, the essentials of human genome sequencing and its consequences will also be discussed. Let us begin our discussion by first understanding the structure of the most interesting molecule in the living system, that is, the DNA. In subsequent sections, we will understand that why it is the most abundant genetic material, and what its relationship is with RNA. 5.1 THE DNA DNA is a long polymer of deoxyribonucleotides. The length of DNA is usually defined as number of nucleotides (or a pair of nucleotide referred to as base pairs) present in it. This also is the characteristic of an organism. For example, a bacteriophage known as φ ×174 has 5386 nucleotides, Bacteriophage lambda has 48502 base pairs (bp), Escherichia coli has 4.6 × 106 bp, and haploid content of human DNA is 3.3 × 109 bp. Let us discuss the structure of such a long polymer. 5.1.1 Structure of Polynucleotide Chain Let us recapitulate the chemical structure of a polynucleotide chain (DNA or RNA). A nucleotide has three components – a nitrogenous base, a pentose sugar (ribose in case of RNA, and deoxyribose for DNA), and a phosphate group. There are two types of nitrogenous bases – Purines (Adenine and Guanine), and Pyrimidines (Cytosine, Uracil and Thymine). Cytosine is common for both DNA and RNA and Thymine is present in DNA. Uracil is present in RNA at the place of Thymine. A nitrogenous base is linked to the OH of 1' C pentose sugar through a N-glycosidic linkage to form a nucleoside, such as adenosine or deoxyadenosine, guanosine or deoxyguanosine, cytidine or deoxycytidine and uridine or deoxythymidine. When a phosphate group is linked to OH of 5' C of a nucleoside through phosphoester linkage, a corresponding nucleotide (or deoxynucleotide depending upon the type of sugar present) is formed. Two nucleotides are linked through 3'-5' phosphodiester linkage to form a dinucleotide. More nucleotides can be joined in such a manner to form a polynucleotide chain. A polymer thus formed has at one end a free 80 Figure 5.1 A Polynucleotide chain 2024-25 MOLECULAR BASIS OF INHERITANCE phosphate moiety at 5' -end of sugar, which is referred to as 5’-end of polynucleotide chain. Similarly, at the other end of the polymer the sugar has a free OH of 3' C group which is referred to as 3' - end of the polynucleotide chain. The backbone of a polynucleotide chain is formed due to sugar and phosphates. The nitrogenous bases linked to sugar moiety project from the backbone (Figure 5.1). In RNA, every nucleotide residue has an additional –OH group present at 2' -position in the ribose. Also, in RNA the uracil is found at the place of thymine (5-methyl uracil, another chemical name for thymine). DNA as an acidic substance present in nucleus was first identified by Friedrich Meischer in 1869. He named it as ‘Nuclein’. However, due to technical limitation in isolating such a long polymer intact, the elucidation of structure of DNA remained elusive for a very long period of time. It was only in 1953 that James Watson and Francis Crick, based on the X-ray diffraction data produced by Maurice Wilkins and Rosalind Franklin, 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 also based on the observation of Erwin Chargaff that for a double stranded DNA, the ratios between Adenine and Thymine and Guanine and Cytosine are constant and equals one. 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. Also, if each strand from a DNA (let us call it as a parental DNA) acts as a template for synthesis of a new strand, the two double stranded DNA (let us call them as daughter DNA) thus, produced would be identical to the parental DNA molecule. Because of this, the genetic implications of the structure of DNA became very clear. The salient features of the Double-helix structure of DNA are as follows: (i) It is made of two polynucleotide chains, where the backbone is constituted by sugar-phosphate, and the bases project inside. (ii) The two chains have anti-parallel polarity. It means, if one chain has the polarity 5' à3' , the other has 3 ' à5 '. (iii) The bases in two strands are paired through hydrogen bond (H-bonds) forming base pairs (bp). Adenine forms two hydrogen bonds with Thymine from opposite strand and vice-versa. Similarly, Guanine is bonded with Cytosine with three H-bonds. As a result, always a purine comes opposite to a pyrimidine. This 81 generates approximately uniform distance between the two strands of the helix (Figure 5.2). (iv) The two chains are coiled in a right-handed fashion. The pitch of the helix is 3.4 nm (a nanometre is one billionth of a metre, that is 10-9 m) and there are roughly 10 bp in each 2024-25  BIOLOGY Figure 5.2 Double stranded polynucleotide chain turn. Consequently, the distance between a bp in a h e l i x i s approximately 0.34 nm. (v) The plane of one base pair stacks over the other in double helix. This, in addition to H-bonds, confers stability of the helical structure (Figure 5.3). Compare the structure of purines and pyrimidines. Can you find out why the distance between two polynucleotide chains in DNA remains almost constant? The proposition of a double helix structure for DNA and its simplicity in explaining the genetic implication became revolutionary. Very soon, Francis Crick proposed the Central dogma in molecular biology, which states that the genetic Figure 5.3 DNA double helix information flows from DNAàRNAàProtein. 82 Central dogma 2024-25