Molecular Basis of Inheritance: DNA

The molecular basis of inheritance is centered around DNA (deoxyribonucleic acid), the genetic material that carries the instructions for the development, functioning, and reproduction of all living organisms. The structure and function of DNA are fundamental to the principles of inheritance, and understanding its role has been a cornerstone of modern genetics, molecular biology, and biotechnology.

1. What is DNA?

DNA is a macromolecule composed of long chains of nucleotides, the building blocks of nucleic acids. It is typically found in the nucleus of eukaryotic cells (in chromosomes) and the cytoplasm of prokaryotic cells. DNA serves as the blueprint for the synthesis of proteins, which are essential for virtually all cellular functions. It carries genetic information across generations and is responsible for the transmission of traits in living organisms.

The structure of DNA is a double helix, which was first described by James Watson and Francis Crick in 1953, based on X-ray diffraction data provided by Rosalind Franklin and Maurice Wilkins. This discovery revolutionized our understanding of genetics and molecular biology.

2. The Structure of DNA

DNA is composed of nucleotides, each consisting of three components:

• A phosphate group
• A deoxyribose sugar molecule (in contrast to RNA, which contains ribose)
• A nitrogenous base

There are four types of nitrogenous bases in DNA:

• Adenine (A): Purine base
• Thymine (T): Pyrimidine base
• Cytosine (C): Pyrimidine base
• Guanine (G): Purine base

These bases pair in specific ways: adenine pairs with thymine (A-T), and cytosine pairs with guanine (C-G). These pairings are held together by hydrogen bonds: two bonds between A and T, and three bonds between C and G. This complementary base pairing is crucial for the accuracy of DNA replication.

The sugar and phosphate groups form the backbone of the DNA strand, and the nitrogenous bases extend inward, forming base pairs that hold the two strands of DNA together. The two strands of DNA run in opposite directions (antiparallel orientation), which is key for processes like DNA replication.

3. DNA Replication

DNA replication is a highly regulated process in which a cell duplicates its DNA before cell division. This ensures that each daughter cell receives an identical copy of the genetic material. Replication occurs in the S phase of the cell cycle and involves several key enzymes and steps:

1. Helicase unwinds the double helix by breaking the hydrogen bonds between base pairs, creating two single-stranded templates.
2. Single-strand binding proteins (SSBs) stabilize the unwound DNA.
3. The enzyme primase synthesizes a short RNA primer, which provides a starting point for DNA synthesis.
4. DNA polymerase then adds complementary nucleotides to the exposed bases, synthesizing a new strand in the 5′ to 3′ direction. This is done on both strands of the DNA, though the two strands are replicated in slightly different ways:
   • The leading strand is synthesized continuously in the same direction as the unwinding of the DNA.
   • The lagging strand is synthesized discontinuously in short fragments known as Okazaki fragments, which are later joined by DNA ligase.
5. After the entire DNA molecule has been replicated, the RNA primers are removed, and the gaps are filled in with DNA nucleotides.

The result of DNA replication is two identical DNA molecules, each consisting of one old strand and one new strand—this is known as semiconservative replication.

4. Genetic Code and Protein Synthesis

The information stored in DNA is used to synthesize proteins through the processes of transcription and translation.

• Transcription: The first step of protein synthesis is the transcription of DNA into messenger RNA (mRNA). This process occurs in the nucleus of eukaryotic cells.
  • RNA polymerase binds to a region of DNA called the promoter and begins synthesizing a complementary strand of RNA.
  • In RNA, the base uracil (U) replaces thymine (T), so adenine (A) pairs with uracil (U) instead of thymine.
  • The RNA strand is synthesized in the 5′ to 3′ direction, and once the entire gene is transcribed, the mRNA is processed (in eukaryotes) by adding a 5′ cap, splicing out introns (non-coding regions), and adding a 3′ poly-A tail.
• Translation: The mRNA is transported out of the nucleus and into the cytoplasm, where it is translated into a protein. Translation occurs in ribosomes, which are made up of ribosomal RNA (rRNA) and proteins. The mRNA is read in sets of three nucleotides, called codons, each of which specifies a particular amino acid.
  • Transfer RNA (tRNA) molecules bring the corresponding amino acids to the ribosome based on the codons in the mRNA. Each tRNA has an anticodon that pairs with a specific mRNA codon.
  • As the ribosome moves along the mRNA, the tRNAs add amino acids to a growing polypeptide chain, which eventually folds into a functional protein.

5. Mutations and Genetic Variation

Mutations are changes in the DNA sequence. They can occur spontaneously due to errors in DNA replication or be induced by environmental factors such as radiation or chemicals. Mutations can have various effects:

• Point mutations: A change in a single nucleotide, which can result in a silent, missense, or nonsense mutation.
  • Silent mutations do not affect the protein because of the redundancy in the genetic code.
  • Missense mutations result in a different amino acid being incorporated into the protein, which can alter its function.
  • Nonsense mutations introduce a premature stop codon, potentially leading to a truncated, nonfunctional protein.
• Frameshift mutations: Inserting or deleting nucleotides can shift the reading frame of the codons, leading to widespread changes in the resulting protein.

Mutations are a source of genetic variation, which is essential for the process of evolution. If a mutation occurs in a germ cell (sperm or egg), it can be passed on to the next generation, contributing to genetic diversity.

6. DNA and Inheritance

The way DNA is inherited is governed by the principles of Mendelian genetics. In sexually reproducing organisms, DNA is inherited from both parents, and each offspring receives a combination of alleles (alternative forms of a gene) from the mother and father.

• Homozygous: An individual has two identical alleles for a particular gene.
• Heterozygous: An individual has two different alleles for a particular gene.

The inheritance of these alleles follows Mendel’s laws:

• Law of Segregation: Each individual has two alleles for each gene, which separate during gamete formation, so each gamete carries only one allele for each gene.
• Law of Independent Assortment: Genes located on different chromosomes assort independently during gamete formation.

Genetic recombination during meiosis further increases genetic diversity by shuffling alleles between chromosomes. This recombination, along with mutations, is a major source of variation in populations.

7. DNA Repair and Maintenance

DNA is constantly exposed to damage from both internal and external sources. To maintain the integrity of the genetic material, cells have evolved several mechanisms for DNA repair. These repair mechanisms can correct errors in DNA replication or fix damage caused by environmental factors.

Key DNA repair processes include:

• Base excision repair: Corrects damage to individual bases (e.g., deamination or oxidation).
• Nucleotide excision repair: Fixes larger regions of DNA that have been damaged, such as by ultraviolet (UV) radiation, by removing a section of the DNA strand and filling in the gap.
• Mismatch repair: Fixes errors that occur during DNA replication, such as mispaired bases.
• Double-strand break repair: If the DNA double helix is broken, repair mechanisms like non-homologous end joining or homologous recombination can be used to repair the breaks.

DNA repair is critical for maintaining genome stability, and defects in repair mechanisms can lead to diseases such as cancer.

8. Applications of DNA Knowledge

The study of DNA has led to numerous advances in medicine, agriculture, and forensic science. Some key applications include:

• Gene therapy: Introducing or altering genes to treat or prevent diseases.
• Genetic engineering: Modifying organisms to produce desired traits, such as genetically modified crops or animals.
• DNA fingerprinting: Used in forensic science to identify individuals based on their unique DNA profiles.
• CRISPR-Cas9: A revolutionary tool for editing genes with precision, offering new possibilities for genetic research and treatment of genetic disorders.

Questions Molecular basis of Inheritance and DNA

1. What is DNA, and why is it important for inheritance?

Answer:
DNA (deoxyribonucleic acid) is the molecule that carries the genetic instructions used in the growth, development, functioning, and reproduction of all living organisms. It is composed of two strands that form a double helix structure. DNA stores genetic information in sequences of nucleotides, which are the building blocks of genes. Each gene codes for a specific protein or functional RNA, and these proteins carry out most functions within cells. DNA is essential for inheritance because it is passed from one generation to the next during reproduction, allowing offspring to inherit traits from their parents.

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2. What is the structure of DNA?

Answer:
The structure of DNA is described as a double helix, which resembles a twisted ladder. It consists of two long strands of nucleotides running in opposite directions (antiparallel), with each nucleotide containing a phosphate group, a deoxyribose sugar, and one of four nitrogenous bases: adenine (A), thymine (T), cytosine (C), and guanine (G). These bases pair in a specific manner: adenine pairs with thymine (A-T), and cytosine pairs with guanine (C-G). The sugar-phosphate backbone of the strands is held together by covalent bonds, while the base pairs are connected by hydrogen bonds. This structure allows DNA to replicate accurately and store genetic information.

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3. How does DNA replication occur?

Answer:
DNA replication is the process by which a cell makes an identical copy of its DNA before cell division. The process involves several steps:

1. Unwinding: The enzyme helicase unwinds the double helix and separates the two strands of DNA by breaking the hydrogen bonds between complementary base pairs.
2. Primer Binding: The enzyme primase synthesizes short RNA primers that provide a starting point for DNA synthesis.
3. Elongation: DNA polymerase adds nucleotides to the growing DNA strand, complementary to the template strand, in the 5′ to 3′ direction.
4. Leading and Lagging Strands: On the leading strand, DNA is synthesized continuously. On the lagging strand, synthesis occurs in short segments known as Okazaki fragments, which are later joined by DNA ligase.
5. Finalization: The RNA primers are replaced with DNA, and the replication process is completed.

DNA replication is semiconservative, meaning each new DNA molecule consists of one original strand and one newly synthesized strand.

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4. What is the genetic code, and how does it direct protein synthesis?

Answer:
The genetic code is a set of rules that define how sequences of nucleotide bases in DNA (and RNA) correspond to specific amino acids in a protein. The code is read in groups of three nucleotides called codons. Each codon specifies a particular amino acid. For example, the codon AUG codes for methionine, the first amino acid in many proteins.

Protein synthesis occurs in two stages:

1. Transcription: In the nucleus, a segment of DNA is copied into messenger RNA (mRNA) by the enzyme RNA polymerase. The mRNA is a complementary copy of the DNA sequence but with uracil (U) replacing thymine (T).
2. Translation: The mRNA travels to the ribosome in the cytoplasm, where it is translated into a polypeptide chain (protein). Each codon on the mRNA is matched with a complementary anticodon on transfer RNA (tRNA), which carries the appropriate amino acid. The ribosome links the amino acids together to form a protein.

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5. What are mutations, and how do they affect genetic information?

Answer:
A mutation is a change in the DNA sequence. Mutations can occur spontaneously during DNA replication or be induced by environmental factors like radiation or chemicals. Mutations can have different effects on the organism:

• Silent mutations: Do not affect the protein because they do not change the amino acid sequence (often due to redundancy in the genetic code).
• Missense mutations: Change one amino acid in the protein, potentially altering its function.
• Nonsense mutations: Introduce a premature stop codon, leading to a truncated, often nonfunctional protein.
• Frameshift mutations: Result from the insertion or deletion of nucleotides, causing a shift in the reading frame and altering the entire downstream protein sequence.

Mutations can introduce genetic variation, which may be beneficial, neutral, or harmful.

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6. What is the difference between DNA and RNA?

Answer:
DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are both nucleic acids that play key roles in cellular functions, but they differ in several important ways:

• Sugar: DNA contains deoxyribose, whereas RNA contains ribose. Ribose has an extra hydroxyl group (-OH) on its 2′ carbon.
• Structure: DNA is double-stranded, forming a double helix, while RNA is single-stranded.
• Bases: DNA uses thymine (T), while RNA uses uracil (U) instead. RNA also uses adenine (A), cytosine (C), and guanine (G).
• Function: DNA stores genetic information, while RNA plays a role in protein synthesis (mRNA) and can also have structural and catalytic functions (e.g., rRNA and tRNA).

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7. How is genetic information inherited from parents to offspring?

Answer:
Genetic information is inherited through the transmission of DNA from parents to offspring. In sexually reproducing organisms, each parent contributes one set of chromosomes, containing genes, to their offspring. The offspring inherit one copy of each gene from each parent, which results in a combination of alleles (different forms of a gene). This inheritance follows Mendelian genetics, where dominant and recessive alleles determine traits.

• Homozygous: An individual has two identical alleles for a gene.
• Heterozygous: An individual has two different alleles for a gene.

The combination of alleles determines the phenotype (observable traits) of the organism. The inheritance of genes follows Mendel’s laws, such as the Law of Segregation and the Law of Independent Assortment.

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8. What is genetic recombination, and how does it increase genetic diversity?

Answer:
Genetic recombination is the process by which genetic material is exchanged between homologous chromosomes during meiosis, the cell division process that produces gametes (sperm and eggs). This occurs during prophase I of meiosis through a process called crossing over, where sections of chromatids from homologous chromosomes break off and exchange places.

Genetic recombination increases genetic diversity by creating new combinations of alleles. As a result, offspring inherit a unique set of genes, which can provide advantages in terms of survival and adaptation to changing environments.

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9. What is the role of enzymes in DNA replication?

Answer:
Enzymes play crucial roles in DNA replication, ensuring that the process is accurate and efficient:

1. Helicase: Unwinds the double helix by breaking the hydrogen bonds between base pairs, creating single-stranded DNA templates.
2. Primase: Synthesizes short RNA primers to provide a starting point for DNA polymerase to begin adding nucleotides.
3. DNA polymerase: Adds nucleotides to the growing DNA strand, ensuring base pairing is correct. It also proofreads the newly synthesized DNA to correct errors.
4. Ligase: Joins the Okazaki fragments on the lagging strand to form a continuous strand.
5. Topoisomerase: Relieves tension ahead of the replication fork by making temporary cuts in the DNA strand to prevent supercoiling.

These enzymes work together to ensure the fidelity and efficiency of DNA replication.

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10. What is CRISPR, and how does it relate to DNA?

Answer:
CRISPR-Cas9 is a powerful tool for editing genes at specific locations in the DNA of living organisms. It is based on a natural defense mechanism in bacteria, where CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) sequences and the associated Cas9 protein protect against viral infections by cutting viral DNA. Scientists have adapted this system for targeted gene editing.

• How CRISPR works: The Cas9 protein is guided by an RNA molecule that matches a specific DNA sequence in the genome. Once the target DNA sequence is identified, Cas9 cuts the DNA at that location. The cell then attempts to repair the break, allowing researchers to insert, delete, or modify genes at the targeted site.

Index NCERT 12th Class Biology