Gene Expression (1)

Gene Expression Overview

• Definition: Gene expression is the intricate biological process through which specific genes are activated to produce gene products, primarily proteins, thereby determining cellular function and organismal traits.

• Importance: It is fundamental to all biological processes, including growth, development, and response to environmental stimuli, and plays a critical role in cellular differentiation and adaptation.

What is a Protein?

• Definition: Proteins are organic macromolecules essential for numerous biological functions including structural components, enzymatic activity, and immune responses.

• Monomer: The basic building blocks of proteins are amino acids, which link together in specific sequences to form polypeptides.

Examples of Protein Functions:

• Muscle Contraction: Proteins like actin and myosin facilitate movement by contracting and relaxing muscle fibers.

• Enzymes in Metabolism: Enzymes, such as amylase and lipase, catalyze biochemical reactions, speeding up metabolic processes crucial for cellular function.

• Immunity: Antibodies are specialized proteins that identify and neutralize pathogens such as bacteria and viruses, playing a pivotal role in the immune response.

• Cell Communication: Hormones and receptor proteins facilitate communication between cells, allowing for coordination and regulation of physiological processes.

Amino Acids

• Diversity: There are 20 different types of amino acids that combine in various sequences to create an immense variety of proteins.

• Basic Core Structure: All amino acids share a general structure:

  • Central Carbon (C) linked to:

    • Amino Group (NH2)

    • Carboxyl Group (COOH)

    • Hydrogen (H)

    • Unique Side Chain (R group): This side chain is what distinguishes one amino acid from another and determines its properties.

• Significance of Order: The order and type of amino acids in a protein influence its three-dimensional shape and ultimately its function.

Protein Structure and Function

• Influence of Order: Changing the type and order of amino acids alters a protein's structure, impacting its functionality and biological role.

• 3D Folding: The interactions among amino acids, including hydrogen bonds, ionic bonds, and Van der Waals forces, dictate the protein’s folding pattern.

• Example of Functional Proteins: Different proteins have distinctly different shapes due to variations in amino acid sequences which affect their interactions and functions, such as enzymes that require specific shapes to bind substrates effectively.

Key Takeaway

• Protein Shape Determines Function: The specific arrangement of amino acids influences the protein's shape, and thus its ability to perform its designated functions. The sequence of nucleotides in DNA encodes the order of amino acids in proteins, demonstrating the link between genetics and protein function.

Case Study: Antithrombin Protein

• Function: Antithrombin regulates blood flow by inhibiting coagulation, preventing the formation of unnecessary blood clots.

• Gene Involvement: Its structure and function are determined by the SERPINC1 gene; mutations in this gene can lead to improper folding of the protein, resulting in potential health issues such as heart attacks or strokes.

Genetics Basics

• Gene Location: The SERPINC1 gene is located on chromosome 1 and encodes the antithrombin protein.

• Alleles: Different versions (alleles) of this gene arise due to variations in nucleotide sequences, causing variations in protein forms and associated functionalities.

Gene Structure

• Two Main Components: Genes are composed of:

  • Regulatory Sequence: This part acts as an on/off switch, controlling the timing and level of gene expression.

  • Coding Sequence: This section carries the DNA instructions for the type and order of amino acids in a protein, determining its structure and functionality.

Gene Expression Process (Central Dogma of Biology)

• Transcription: The process where DNA is transcribed into messenger RNA (mRNA) occurs in the nucleus and is facilitated by the enzyme RNA Polymerase.

• Translation: The translation process involves translating mRNA into a polypeptide chain of proteins, occurring in the cytoplasm at ribosomes where the ribosome reads the mRNA and synthesizes proteins using transfer RNA (tRNA).

RNA Structure and Function

• RNA (Ribonucleic Acid): This molecule differs from DNA by having ribose sugar, a phosphate group, and nitrogenous bases, including uracil (instead of thymine in DNA).

• Functions of RNA:

  • Acts as a messenger (mRNA)

  • Functions as a transfer molecule (tRNA)

  • Serves as a structural component of ribosomes (rRNA)

Steps of Transcription

• Initiation: RNA polymerase binds to the promoter region of the DNA and unwinds the double helix.

• Elongation: RNA polymerase reads the DNA template strand, synthesizing a complementary RNA strand (mRNA) by adding nucleotides based on base-pairing rules.

Steps of Translation

• Initiation: The ribosome attaches to mRNA at the start codon (AUG), signaling the beginning of protein synthesis.

• Elongation: The ribosome moves along the mRNA, reading each codon and matching it with the appropriate tRNA carrying specific amino acids, forming a growing polypeptide chain.

• Termination: The ribosome reaches a stop codon (UAA, UAG, UGA), signaling the end of protein synthesis, leading to the disassembly of the ribosomal components.

Types of RNA

• mRNA: Carries the genetic information from DNA in the nucleus to the ribosome for protein synthesis.

• tRNA: Transfers specific amino acids to the ribosome during protein synthesis, ensuring the correct translation of the mRNA codons.

• rRNA: A key structural component of the ribosome, aiding in the assembly and synthesis of proteins.

Mutations in Genetic Material

• Mutations: These are changes in the DNA sequence that can significantly affect the structure and function of proteins.

• Examples of Mutations:

  • Point Mutations: Change in a single nucleotide, which can result in a different amino acid in the protein sequence.

  • Frameshift Mutations: Insertion or deletion of nucleotides that shift the reading frame of the gene, potentially alter the entire amino acid sequence downstream.

• Importance of Mutations: While some mutations can lead to diseases, others contribute to genetic diversity, which is essential for evolution and adaptation of populations.

Case Study: Pharming

• Definition: Pharming refers to the use of genetically modified organisms (GMOs) to produce pharmaceuticals, offering a novel approach to drug production.

• Example: Transgenic goats have been engineered to secrete antithrombin proteins in their milk, which can be harvested and purified for therapeutic uses in humans.

Conclusion

• A comprehensive understanding of gene expression is critical in biology as it interlinks genetics, protein functionality, and the consequences of genetic variations on health and disease outcomes.