UPSC MainsMEDICAL-SCIENCE-PAPER-I202310 Marks
Q8.

Define Genetic code and explain the Wobble Hypothesis. Discuss briefly the post-translational modifications of proteins.

How to Approach

This question requires a detailed understanding of molecular biology, specifically the genetic code, the wobble hypothesis, and post-translational modifications. The answer should begin with a clear definition of the genetic code, followed by a thorough explanation of the wobble hypothesis, including its significance. Finally, it should discuss various post-translational modifications, providing examples. A structured approach, utilizing headings and subheadings, will enhance clarity. Focus on explaining the 'how' and 'why' of each process.

Model Answer

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Introduction

The central dogma of molecular biology describes the flow of genetic information from DNA to RNA to protein. The genetic code is the set of rules by which this information is translated into amino acids, the building blocks of proteins. However, the relationship between codons and amino acids isn’t always strict, a phenomenon explained by the wobble hypothesis. Furthermore, proteins rarely function in their nascent form and undergo various post-translational modifications that are crucial for their activity, localization, and interactions. This answer will define the genetic code, explain the wobble hypothesis, and discuss the key post-translational modifications of proteins.

Genetic Code: Definition and Characteristics

The genetic code is a set of instructions that living cells use to translate information encoded within genetic material (DNA or RNA sequences) into proteins. It consists of triplets of nucleotides, called codons, each specifying a particular amino acid or a stop signal. Key characteristics include:

  • Universality: The code is nearly universal across all organisms, from bacteria to humans.
  • Degeneracy/Redundancy: Most amino acids are specified by more than one codon. This provides some protection against mutations.
  • Non-overlapping: Codons are read sequentially, without overlap.
  • Commaless: There are no intervening nucleotides between codons.
  • Ambiguity: Some codons can code for multiple amino acids under specific conditions.

The Wobble Hypothesis

Proposed by Francis Crick in 1966, the wobble hypothesis explains how a limited number of tRNA molecules can recognize more than one codon. It posits that the base pairing rules are relaxed at the third position (3’ end) of the codon, allowing for “wobble” in the interaction between the codon and anticodon.

Specifically, the first two bases of the codon follow the standard Watson-Crick base pairing rules (A-U, G-C). However, the third base can pair with multiple possibilities. For example, inosine (I), a modified nucleoside found in tRNA, can base pair with U, C, or A. This allows a single tRNA to recognize multiple codons differing only in their third base.

Significance: The wobble hypothesis reduces the number of tRNA molecules required for translation, making the process more efficient. It also explains why certain mutations in the third position of a codon are often silent (do not alter the amino acid sequence).

Post-Translational Modifications of Proteins

After a polypeptide chain is synthesized by ribosomes, it undergoes various post-translational modifications (PTMs) that are essential for its proper folding, stability, activity, and localization. These modifications can be enzymatic or spontaneous. Some key PTMs include:

  • Phosphorylation: Addition of a phosphate group to serine, threonine, or tyrosine residues. Regulates protein activity and signaling pathways. (e.g., activation of kinases).
  • Glycosylation: Addition of carbohydrate moieties. Important for protein folding, stability, and cell-cell recognition. (e.g., glycoproteins on cell surfaces).
  • Ubiquitination: Addition of ubiquitin, a small protein. Marks proteins for degradation or alters their function.
  • Acetylation: Addition of an acetyl group, often to lysine residues. Affects gene expression and protein-protein interactions.
  • Methylation: Addition of a methyl group. Can alter protein function or regulate gene expression.
  • Proteolytic Cleavage: Cleavage of the polypeptide chain by proteases. Activates pro-enzymes (e.g., proinsulin to insulin) or removes signal peptides.
  • Lipidation: Addition of lipid molecules. Anchors proteins to cell membranes.

The combination of PTMs a protein receives determines its final structure and function. Dysregulation of PTMs is often associated with diseases like cancer and neurodegenerative disorders.

Modification Enzyme Involved Effect
Phosphorylation Kinases Activation/Inactivation, conformational change
Glycosylation Glycosyltransferases Protein folding, stability, cell signaling
Ubiquitination Ubiquitin ligases Protein degradation, altered function

Conclusion

In conclusion, the genetic code provides the blueprint for protein synthesis, while the wobble hypothesis explains the flexibility in codon-anticodon interactions. However, the journey from a polypeptide chain to a functional protein is completed through a diverse array of post-translational modifications. These modifications are crucial for regulating protein activity, localization, and interactions, ultimately determining cellular function and organismal health. Understanding these processes is fundamental to comprehending the complexities of biological systems and developing targeted therapies for various diseases.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Codon
A sequence of three nucleotides in DNA or RNA that specifies a particular amino acid or a stop signal during protein synthesis.
Anticodon
A sequence of three nucleotides in a tRNA molecule that is complementary to a codon in mRNA, allowing for the correct amino acid to be added to the growing polypeptide chain.

Key Statistics

There are 64 possible codons (4^3) in the genetic code, but only 20 standard amino acids.

Source: Molecular Biology of the Gene (Watson et al., 2014)

Approximately 85% of eukaryotic proteins undergo some form of post-translational modification.

Source: Nature Reviews Molecular Cell Biology (2010)

Examples

Phenylketonuria (PKU)

PKU is a genetic disorder caused by a deficiency in the enzyme phenylalanine hydroxylase. This enzyme requires post-translational hydroxylation for activity. Without proper hydroxylation, the enzyme is non-functional, leading to a buildup of phenylalanine.

Frequently Asked Questions

What is the significance of the degeneracy of the genetic code?

The degeneracy of the genetic code minimizes the impact of point mutations. If a mutation occurs in the third position of a codon, it may not result in a change in the amino acid sequence due to wobble pairing, thus preserving protein function.

Topics Covered

BiochemistryGeneticsDNARNAProtein Synthesis