Chromosome Structure & Transposition

Driving Questions on Chromosome Structure

  • How are prokaryotic and eukaryotic chromosomes structured?

  • What processes govern chromosome structure?

  • How does genomic and chromosome structure change?

Chromosome Structure Overview

Basic Definitions

  • Chromosomes: Structures that contain the genetic material.

  • Genome: The complete set of genetic material that an organism possesses.

    • In bacteria: Typically a single circular chromosome.

    • In eukaryotes: A nuclear genome refers to one complete set of nuclear chromosomes.

    • Notable exceptions: Eukaryotes also possess a mitochondrial genome; plants contain both a mitochondrial and a chloroplast genome.

Function of Genetic Material

  • Primary Function: Store information necessary to produce an organism.

  • DNA Molecule Functionality:

    • Through its base sequence, DNA sequences are necessary for:

    1. Synthesis of RNA and cellular proteins.

    2. Replication of chromosomes.

    3. Proper segregation of chromosomes.

    4. Compaction of chromosomes to fit within the cell.

Bacterial Chromosomes

Structure and Composition

  • Typical Structure: Circular DNA molecule, a few million base pairs long.

  • Examples:

    • Escherichia coli: ~4.6 million base pairs.

    • Haemophilus influenzae: ~1.8 million base pairs.

  • Typical bacterial chromosome contains a few thousand genes, mainly protein-encoding genes (structural genes).

  • Nontranscribed DNA segments between genes are termed intergenic regions.

  • Repetitive sequences: May play a role in DNA folding, gene regulation, and genetic recombination.

  • Origin of replication: The initiation site for DNA replication.

Compaction of Bacterial Chromosomes

Overview

  • Chromosomal DNA must be compacted about 1000-fold to fit within bacterial cells.

  • Nucleoid: The region where the bacterial chromosome is found, not surrounded by a membrane - the DNA is in direct contact with the cytoplasm.

Structures in Compaction

  • The bacterial chromosome has a central core from which loops called microdomains emanate.

    • Typical length of microdomains: 10,000 base pairs (E. coli has 400 to 500 microdomains).

    • Adjacent microdomains organize into larger structures called macrodomains (800 to 1000 kbp long).

  • Nucleoid-associated proteins (NAPs) aid in forming these domains and assist in bending DNA or bridging between DNA regions.

DNA Supercoiling

Explanation of Supercoiling

  • Supercoiling: Twisting forces change the conformation of DNA, where additional coils form due to twisting forces.

  • This phenomenon results in DNA structures differing in supercoiling being called topoisomers.

  • Types of Supercoiling:

    • Negative supercoiling: Causes compaction and creates tension, facilitating DNA strand separation in E. coli (one negative supercoil per 40 turns of the double helix).

    • Positive supercoiling: Involves more turns and is generally less favorable in biological systems.

Control of Supercoiling

  • Enzymes Involved:

    • DNA gyrase (topoisomerase II): Introduces negative supercoils using ATP.

    • DNA topoisomerase I: Relaxes negative supercoils by breaking one strand and allowing it to rotate.

  • The interplay between these enzymes governs overall supercoiling of bacterial DNA.

Drug Targeting of Supercoiling Enzymes

  • Clinical Implications: The action of DNA gyrase is crucial for bacterial survival, making it a target for antibiotic therapies.

Eukaryotic Chromosomes

Structural Differences from Bacteria

  • Eukaryotic chromosomes are linear, typically found in sets, and can range from tens of millions to hundreds of millions of base pairs in length.

  • Eukaryotic chromosomes are located in the nucleus and often contain many origins of replication.

  • Centromere: A constricted region essential for chromosome segregation during cell division.

  • Kinetochore proteins: Link the centromere to the spindle apparatus during mitosis and meiosis.

  • Telomeres: Located at the ends of chromosomes, preventing translocations and maintaining chromosome length.

Gene Composition in Eukaryotic Chromosomes

  • Genes are typically located between the centromeric and telomeric regions.

    • A single eukaryotic chromosome usually has hundreds to thousands of genes.

    • Eukaryotic gene variability:

    • In organisms like yeast: Genes are smaller, with few introns.

    • In mammals: Genes are longer with many introns, ranging from less than 100 to more than 10,000 base pairs in length.

Variation in Genome Size

Factors Influencing Size

  • Genome sizes vary greatly among species, and this variation is not necessarily related to complexity.

    • Notable example: Closely related salamander species show a two-fold difference in genome size due to repetitive DNA accumulation rather than extra genes.

Sequence Complexity

  • Defined as the frequency of particular base sequences in the genome:

    • Types:

    1. Unique (non-repetitive)

    2. Moderately repetitive

    3. Highly repetitive

Repetitive DNA Sequences

Classification

  • Unique Sequences: Found once or a few times; includes protein-coding genes (approximately 41% in humans).

  • Moderately Repetitive Sequences: Occur a few hundred to thousands of times in the genome, including genes for rRNA and transposable elements.

  • Highly Repetitive Sequences: Found tens of thousands to millions of times; function is not well understood.

Transposable Elements (TEs)

Definition and Overview

  • Transposition: The process where a DNA segment is inserted into a new location within the genome.

  • TEs, also known as “jumping genes,