Molecular Basis of Inheritance - Notes | Class 12

Molecular Basis of Inheritance: The DNA

Nucleic acids (DNA & RNA) are the building blocks of genetic material.
DNA is the genetic material in most of the organisms.
RNA is the genetic material in some viruses. RNA mostly functions as messengers.

THE DNA

Polynucleotides are the polymer of nucleotides.
DNA & RNA are polynucleotides. A nucleotide has 3 components:
- A nitrogenous base.
- A pentose sugar (ribose in RNA & deoxyribose in DNA).
- A phosphate group.
Nitrogen bases are 2 types:
- Purines: It includes Adenine (A) and Guanine (G).
- Pyrimidines: It includes Cytosine (C), Thymine (T) & Uracil (U). Thymine (5-methyl Uracil) present only in DNA and Uracil only in RNA.
A nitrogenous base is linked to the OH of 1' C pentose sugar through an N-glycosidic linkage to form a nucleoside.
Nucleosides in RNA and DNA:
- RNA: Adenosine → DNA: Deoxyadenosine
- RNA: Guanosine → DNA: Deoxyguanosine
- RNA: Cytidine → DNA: Deoxycytidine
- RNA: Uridine → DNA: Deoxythymidine
A phosphate group is linked to OH of 5' C of a nucleoside through a phosphoester linkage to form a nucleotide (or deoxynucleotide).
In RNA, each nucleotide has an additional –OH group at 2' C of the ribose (2'-OH).
2 nucleotides are linked through a 3'-5' phosphodiester bond to form a dinucleotide.
When more nucleotides are linked, it forms a polynucleotide.

Friedrich Meischer (1869): Identified DNA and named it as 'Nuclein'.
James Watson & Francis Crick (1953) proposed a double helix model of DNA. It was based on X-ray diffraction data produced by Maurice Wilkins & Rosalind Franklin.

DNA is made of 2 polynucleotide chains coiled in a right-handed fashion. Its backbone is formed of sugar & phosphates. The bases project inside.
The 2 chains have anti-parallel polarity, i.e., one chain has the polarity 5'→3' and the other has 3'→5'.
The bases in 2 strands are paired through H-bonds forming base pairs (bp).
A=T (2 hydrogen bonds), C≡G (3 hydrogen bonds).
A purine comes opposite to a pyrimidine. This generates uniform distance between the 2 strands.
Erwin Chargaff's rule: In DNA, the proportion of A is equal to T and the proportion of G is equal to C.

∴ [A] + [G] = [T] + [C] or [A] + [G] / [T] + [C] = 1.

Ф 174 (a bacteriophage) has 5386 nucleotides.
Bacteriophage lambda has 48502 base pairs (bp).
E. coli has 4.6x10⁶ bp.
Haploid content of human DNA is 3.3x10⁹ bp.
Length of DNA = number of base pairs × distance between two adjacent base pairs.
Number of base pairs in human = 6.6 x 10⁹.

Hence, the length of DNA = 6.6 x 10⁹ x 0.34 x 10^-9.

= 2.2 m.

∴ The number of base pairs:

$\frac{1.36 \times 10^{- 3}}{0.34 \times 10^{- 9}}$

= 4 x 10⁶ bp.

It is proposed by Francis Crick. It states that the genetic information flows from DNA → RNA → Protein.

Central Dogma of Molecular Biology

In some viruses, the flow of information is in the reverse direction (from RNA to DNA). It is called reverse transcription.

In prokaryotes (e.g., E. coli), the DNA is not scattered throughout the cell. DNA is negatively charged. So it is held with some positively charged proteins to form a nucleoid.
In eukaryotes, there is a set of positively charged, basic proteins called histones.
Histones are rich in positively charged basic amino acid residues lysines and arginines.
8 histones form a histone octamer.
Negatively charged DNA is wrapped around the histone octamer to give a nucleosome.

Nucleosomes constitute the repeating unit to form chromatin. Chromatin is the thread-like stained bodies.
Nucleosomes in chromatin = 'beads-on-string'.
Chromatin is packaged → chromatin fibres → coiled and condensed at metaphase stage → chromosomes.
Higher level packaging of chromatin requires non-histone chromosomal (NHC) proteins.
Chromatin has 2 forms:
- Euchromatin: Loosely packed and transcriptionally active region of chromatin. It stains light.
- Heterochromatin: Densely packed and inactive region of chromatin. It stains dark.