Differential Gene Expression

From One Cell Come Many

  • A miraculous phenomenon of embryonic development.

Conceptual Framework

  • Neil Shubin YIF (Page 117): "Imagine a house coming together spontaneously from all the information contained in the bricks – that is how animal bodies are made."

    • This metaphor illustrates the concept of development where genetic information from smaller components leads to the formation of complex structures.

Genomic Equivalence

  • Definition: Chromosomes in each cell of an organism’s body are the mitotic descendants of the chromosomes established at fertilization (Wilson 1896; Boveri 1904).

    • Each somatic cell nucleus has the same chromosomes, and therefore, the same set of genes.

Anatomy of DNA

  • Referenced in Anatomy and Physiology: The Unity of Form and Function (9th edition) by Kenneth Saladin ©2021.

Chromosomes

  • Definition: A chromosome is a complex of DNA and protein carrying the genetic material of a cell's nucleus.

  • It is typically visible during cell division and is composed of tightly coiled chromatin.

Chromatin

  • Definition: Chromatin is filamentous (non-condensed) DNA complexed with proteins in eukaryotic non-dividing cells.

    • Characteristics: Chromatin is too slender to be seen, except for a granular appearance under a light microscope.

    • Protein Component: Histones constitute about half the weight of chromatin.

    • Nucleosomes: Basic unit of chromatin structure composed of an octamer of histone proteins wrapped with DNA (approximately 147 base pairs of DNA).

Central Dogma of Molecular Biology

  • Steps of Gene Expression:

    1. Transcription: DNA is copied into pre-mRNA.

    2. Processing: The pre-mRNA transcript undergoes modifications.

    3. Transport out of nucleus: Processed mRNA is moved from the nucleus to the cytoplasm.

    4. Translation: mRNA is decoded by ribosomes to synthesize proteins.

    5. Protein folding and modification: The newly formed protein undergoes folding and any required modifications.

  • Illustrated in Developmental Biology (13e).

Gene Anatomy

  • Key Components:

    • Promoter: RNA polymerase II binding site for transcription initiation.

    • Exons: Coding regions that will be translated into proteins.

    • Introns: Non-coding regions that need to be removed before translation.

    • Transcription Termination: Capped sequences and termination codons play critical roles in defining the ends of mRNA.

Differential Gene Expression

  • Definition: The process by which cells become different from one another based on the unique combination of genes that are activated or expressed.

    • Alternative Definition: The process by which the information encoded in a gene is turned into a function.

Postulates of Differential Gene Expression

  1. Every somatic cell nucleus contains the complete genome established in the fertilized egg.

  2. Unused genes are neither destroyed nor mutated; they retain potential for being expressed.

  3. Only a small percentage of the genome is expressed in each cell; a portion of RNA synthesized is specific for that cell type.

Levels of Gene Regulation

  • Gene expression can be regulated at four levels:

    1. Level 1: Regulation of gene transcription.

    2. Level 2: Selective pre-messenger RNA processing.

    3. Level 3: Selective messenger RNA translation.

    4. Level 4: Regulation of posttranslational protein modification.

Level 1: Gene Transcription Regulation

  • Epigenetic Modification of Chromatin: Modifying how a gene is expressed without altering the DNA sequence itself.

Types of Chromatin Modifications

  • Histone Acetylation: Addition of negatively charged acetyl groups; promotes transcription (euchromatin).

  • Histone Methylation: Addition of methyl groups; prevents transcription (heterochromatin); can be heritable.

Example of Chromatin Modification

  • Polycomb Proteins: Act in the repression of genes.

  • Trithorax Proteins: Counteract the effect of Polycomb proteins.

Control with Transcription Factors

  • Transcription factors play essential roles in embryogenesis.

    • Functions:

    • Recruit histone-modifying enzymes.

    • Stabilize the transcription pre-initiation complex for RNA polymerase II binding.

    • Coordinate timed expression of multiple genes.

Floral Development Genes

  • Classes of Genes: A, B, C, D, and E specify floral organ identity. E.g., class B controls whorls 2 and 3 petals and stamens.

  • Arabidopsis thaliana: Example showing formation of flowers.

Level 2: Selective Pre-mRNA Processing

  • The process of cutting, rearranging, and ligating exons to create different combinations that lead to diverse proteins.

  • Gene/Protein Relationship: Approximately 20,000 human genes can produce a larger proteome through splicing isoforms.

Level 3: Selective mRNA Translation

  • mRNA Longevity: Longer persistence of an mRNA increases the amount of protein that can be synthesized, often reliant on the length of the poly A tail.

  • Stored Oocyte mRNAs: Inhibit translation until activated by ion signals during fertilization.

  • Ribosomal Selectivity: Certain ribosomal proteins are necessary to translate specific mRNAs; absence leads to unsuccessful gene expression.

  • MicroRNAs: Can inhibit gene expression by degrading specific mRNAs (loss of poly A tails).

Level 4: Posttranslational Protein Modification

  • Some proteins remain inactive until certain sections are cleaved away; others require assembly with other proteins or binding of ions or modification by groups such as phosphates or acetates.

Summary of Transcription, Processing, and Translation

  • Transcription: In the nucleus, DNA regions are accessible to RNA polymerase II, which transcribes genes into pre-mRNA.

  • Processing: Pre-mRNA undergoes modifications to form mature mRNA.

  • Translation: The mRNA associates with ribosomes, and information is translated into a protein.

  • Protein Folding and Modification: The new protein folds and may undergo further modification, including adding carbohydrate groups.