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Molecular Basis of Inheritance

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Introduction

The molecular basis of inheritance focuses on how genetic information is stored, organised, and transmitted from one generation to the next. This study involves understanding how genes, which are specific segments of DNA found on chromosomes, determine the traits we inherit. In simple terms, it looks at how DNA directs the synthesis of RNA and proteins, allowing living organisms to grow, develop, and reproduce.


Genes and Chromosomes

Genes are the functional units of heredity. They code for specific proteins or RNA molecules that perform various functions in the body. Chromosomes are thread-like structures composed of DNA and proteins. In eukaryotes (such as plants and animals), chromosomes are found in the nucleus, while in prokaryotes (such as bacteria), they are present in the cytoplasm.


DNA: Structure and Key Features

DNA, short for deoxyribonucleic acid, is the main hereditary material in most living organisms and some viruses. It was first identified as an acidic substance by Friedrich Miescher. Later, James Watson and Francis Crick proposed the double-helical model of DNA.


DNA Structure


  1. Composition

    • Nucleotides are the building blocks of DNA. Each nucleotide consists of:

      • A phosphate group

      • A five-carbon sugar (deoxyribose)

      • A nitrogenous base (Adenine, Thymine, Guanine, or Cytosine)

  2. Double-Helical Structure

    • DNA consists of two polynucleotide strands twisted around each other in a helix.

    • The sugar-phosphate backbones of the strands lie on the outside, while the nitrogenous bases project towards the inside.

    • Adenine (a purine) pairs with Thymine (a pyrimidine), and Guanine (a purine) pairs with Cytosine (a pyrimidine). This complementary base pairing is held together by hydrogen bonds.

    • The two strands are antiparallel, meaning one strand runs in the 5′ to 3′ direction and the other in the 3′ to 5′ direction.


For more details, see our DNA Structure page.


Central Dogma

Francis Crick put forward the concept of the central dogma, which describes the flow of genetic information:


  • DNA → RNA → Protein


In typical cells, DNA is first transcribed into RNA, and then RNA is translated into proteins. However, in retroviruses, the flow of information occurs in reverse (RNA → DNA → mRNA → Protein), primarily because they use an enzyme called reverse transcriptase.


DNA Packaging

In eukaryotic cells, DNA is organised with the help of proteins called histones. DNA, which is negatively charged, wraps around a positively charged histone octamer to form a structure known as a nucleosome. A series of these nucleosomes coils further to form chromatin. During cell division, chromatin condenses to form distinct chromosomes.


DNA Replication

One remarkable aspect of DNA is its ability to replicate itself (self-replication). This ensures that each daughter cell receives an identical copy of genetic material.


  • Semi-Conservative Nature: During replication, the double helix unwinds, and each parent strand acts as a template. New nucleotides pair with the exposed bases, forming two new DNA molecules, each with one old (parent) strand and one newly synthesised strand.

  • Replication Fork and Direction: Replication proceeds at sites called replication forks. DNA synthesis always occurs in the 5′ to 3′ direction.

  • Time Frame: In prokaryotes, replication can occur within minutes, while in eukaryotes, it typically takes longer (several hours) and happens during the S-phase of the cell cycle.


For more information, see our DNA Replication page.


RNA and Its Importance

Ribonucleic acid (RNA) is another vital nucleic acid found in all living cells. It often serves as an intermediary between DNA and proteins, but it can also function as genetic material in certain viruses.


  1. Structure

    • RNA contains ribose sugar instead of deoxyribose.

    • It uses the base Uracil (U) instead of Thymine (T).

  2. Types of RNA

    • Messenger RNA (mRNA): Carries coding information from DNA to ribosomes for protein synthesis.

    • Transfer RNA (tRNA): Brings specific amino acids to the ribosome during protein synthesis.

    • Ribosomal RNA (rRNA): Forms the core of ribosomes, which are the sites of protein synthesis.

    • Other types include small nuclear RNA (snRNA), microRNA (miRNA), etc.


See our Structure of RNA page to learn more.


The Genetic Code

The genetic code is a set of rules that defines how a sequence of nucleotides in mRNA is translated into a sequence of amino acids in a polypeptide. Each group of three nucleotides (codon) corresponds to a specific amino acid or a “stop” signal.


  1. Characteristics

    • Triplet: Three nucleotides form a codon.

    • Degenerate: More than one codon can code for the same amino acid.

    • Universal: Almost all organisms use the same code (with a few exceptions).

    • Non-Overlapping and Comma-Less: Codons are read in a continuous, non-overlapping manner.

    • Non-Ambiguous: Each codon specifies only one amino acid (or a stop signal).

  2. Codon Usage

    • Out of 64 possible codons, 61 code for amino acids and 3 act as stop codons.

    • The frequency of each codon’s usage varies among different organisms.


Human Genome Project

The Human Genome Project was an international effort aimed at identifying and mapping all the genes in the human genome. The primary goals included:


  1. Sequencing the Genome

    • Providing a complete sequence of approximately 3 billion base pairs.

  2. Comparative Genomics

    • Sequencing the genomes of model organisms like mice and fruit flies to aid in medical research.

  3. Data Accessibility

    • Developing tools to analyse and share the data widely.

  4. Future Prospects

    • Better understanding of genetic disorders, personalised medicine, and advanced diagnostic tools.


Additional Unique Insights

Introns and Exons

  • Introns: Non-coding regions within a gene that are removed during RNA splicing.

  • Exons: Coding regions that remain in the final mRNA to be translated into proteins.


Telomeres and Telomerase

  • Telomeres: Repetitive nucleotide sequences at the ends of eukaryotic chromosomes, protecting them from damage.

  • Telomerase: An enzyme that helps in adding telomeric repeats to chromosomes in certain cells, allowing them to divide indefinitely (e.g., stem cells).


Quick Quiz

1. Which enzyme synthesises DNA from an RNA template in retroviruses?
A. DNA polymerase
B. Reverse transcriptase
C. RNA polymerase
D. Helicase
Answer: B. Reverse transcriptase


2. Which of the following statements about the genetic code is correct?
A. It is overlapping.
B. It is non-ambiguous.
C. There are 64 amino acids.
D. All codons are stop codons.
Answer: B. It is non-ambiguous


3. Which structure is formed when DNA wraps around histone proteins?
A. Chromosome
B. Nucleosome
C. Chromatid
D. Centromere
Answer: B. Nucleosome

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FAQs on Molecular Basis of Inheritance

1. What is meant by the molecular basis of inheritance?

The molecular basis of inheritance refers to the study of the biochemical nature of genetic material and the processes by which it is stored, replicated, expressed, and transmitted across generations. It primarily focuses on the structure and function of DNA, RNA, and proteins, and how they work together according to the principles of the Central Dogma.

2. What are the three main components of a DNA nucleotide?

A DNA nucleotide, the building block of DNA, consists of three distinct chemical components:

  • A pentose sugar (deoxyribose).
  • A phosphate group, which gives DNA its acidic and negatively charged nature.
  • A nitrogenous base, which can be a purine (Adenine or Guanine) or a pyrimidine (Cytosine or Thymine).

3. What are the key structural and functional differences between DNA and RNA?

DNA and RNA are both nucleic acids, but they differ in several key aspects:

  • Sugar: DNA contains deoxyribose sugar, while RNA contains ribose sugar.
  • Bases: DNA uses the nitrogenous bases Adenine, Guanine, Cytosine, and Thymine (T). In RNA, Thymine is replaced by Uracil (U).
  • Structure: DNA is typically a double-stranded helix, whereas RNA is usually single-stranded.
  • Function: DNA serves as the long-term storage for genetic information, while RNA's primary roles include acting as a messenger (mRNA), transferring amino acids (tRNA), and forming ribosomes (rRNA).

4. What are the primary functions of the three major types of RNA in a cell?

The three major types of RNA each have a specialised role in protein synthesis:

  • Messenger RNA (mRNA): It carries the genetic code transcribed from DNA in the nucleus to the ribosomes in the cytoplasm.
  • Transfer RNA (tRNA): It acts as an adapter molecule, reading the codons on the mRNA and bringing the corresponding amino acid to the ribosome.
  • Ribosomal RNA (rRNA): It is a structural and catalytic component of ribosomes, the cellular machinery where protein synthesis (translation) occurs.

5. How does the 'Central Dogma' of molecular biology explain the flow of genetic information?

The Central Dogma, proposed by Francis Crick, describes the standard directional flow of genetic information within a biological system. It states that information flows from DNA to RNA to Protein. This occurs in two main steps: transcription, where a segment of DNA is copied into mRNA, and translation, where the mRNA sequence is used to build a protein. An exception is seen in retroviruses, which use an enzyme called reverse transcriptase to make DNA from an RNA template.

6. Why is DNA replication described as 'semi-conservative', and which experiment confirmed this?

DNA replication is called semi-conservative because when a DNA molecule replicates, the two strands of the double helix unwind, and each strand serves as a template for a new complementary strand. The result is two new DNA molecules, each containing one original (parental) strand and one newly synthesised strand. This mechanism was experimentally proven by the Meselson and Stahl experiment in 1958.

7. Why is the genetic code described as being degenerate and universal?

The genetic code has these two key properties:

  • Degenerate: This means that a single amino acid can be coded for by more than one codon. For example, the amino acid Leucine is specified by six different codons. This degeneracy provides a buffer against mutation, as a change in the third base of a codon may not change the resulting amino acid.
  • Universal: This means that the same codons specify the same amino acids in almost all organisms, from bacteria to humans. This universality is powerful evidence for a common evolutionary origin of life.

8. How is a very long DNA molecule packaged into a compact chromosome inside a eukaryotic nucleus?

The packaging of DNA is a multi-level process. The negatively charged DNA molecule is wrapped around a core of eight positively charged protein molecules called a histone octamer. This structure, resembling a bead on a string, is called a nucleosome. These nucleosomes are then further coiled and condensed to form a structure called chromatin. During cell division, this chromatin condenses even further to form the visible, highly compact structures known as chromosomes.

9. What is the functional difference between exons and introns in a eukaryotic gene?

In eukaryotic genes, the coding sequences are not continuous. Exons are the regions of a gene that are expressed, meaning they contain the code for the final protein. Introns are non-coding, intervening sequences that are present in the initial RNA transcript but are removed through a process called RNA splicing. Only the exons are joined together to form the mature mRNA that is translated into a protein.

10. What were the main goals and one major application of the Human Genome Project (HGP)?

The main goals of the Human Genome Project were to identify all the genes in human DNA, determine the sequence of the 3 billion chemical base pairs that make up human DNA, and store this information in databases. A major application of this knowledge is in the field of medicine, where it helps in diagnosing genetic disorders, understanding diseases like cancer, and developing personalised medicine tailored to an individual's genetic makeup.


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