BioMed Foundation

< All Topics

5.02 Chromosomes

Posted10/11/2024
Updated21/12/2024
ByBMF
Views68

Diagram of a replicated and condensed metaphase eukaryotic chromosome: 1, Chromatid, 2. Centromere, 3. Short arm, 4. Long arm.

Key Concepts:

  • Chromosomes:
    • Threadlike structures visible in the nucleus just before cell division.
    • Named from “chromo” (colored) and “somes” (bodies) due to intense staining.
  • Species-Specific: Number of chromosomes varies by species (e.g., humans have 46, fruit flies have 8).

Chromosome Structure:

  • Basic Components:
    • Made up of two identical chromatids, known as sister chromatids.
      • Each chromatid contains one DNA molecule.
      • Chromatids are connected by a centromere.
  • Centromere:
    • Holds sister chromatids together.
    • Position on the chromosome is consistent for each specific chromosome.
  • Telomeres:
    • Protective ends of chromosomes, essential for successful division.
  • Genetic Composition:
    • DNA Molecule:
      • Each chromatid has a single DNA molecule, which holds genetic information.
      • Genes (units of inheritance) are located along the DNA. A gene is a sequence of nucleotides that forms part of a DNA molecule, and that codes for a polypeptide or protein.
      • Genetic Identity:
        • Sister chromatids are genetically identical, ensuring precise distribution during cell division.
        • One chromatid is allocated to each daughter cell, maintaining genetic consistency.

A mitotic chromosome observed in high-voltage TEM. 

DNA Packing and Chromatin:

  • DNA Length and Nucleus Size:
    • DNA is compacted to fit within the nucleus.
      • E.g., 1.8 meters of DNA in a human cell fits into a nucleus about 6 μm in diameter.
      • Packing ratio reflects the level of DNA compaction.
  • Role of Proteins in Compaction:
    • Histones: Basic proteins around which DNA is wound.
      • Essential for DNA compaction; DNA and histones form chromatin.
      • Chromatin makes up chromosomes and helps prevent DNA tangling.
  • Histone Conservation:
    • Histones are highly conserved in evolution, indicating a crucial role in DNA packaging and stability.

Nucleosome

Definition

  • The nucleosome is the basic structural and functional unit of chromatin, which packages and organizes DNA within the nucleus of eukaryotic cells.

Structure

Histone Octamer:

  • Consists of 8 histone proteins:
    • 2 copies each of:
      • H2A
      • H2B
      • H3
      • H4
  • These histones are positively charged to interact with the negatively charged DNA backbone.

Nucleosomes wrapped around DNA. Two copies of the four core histone proteins H2A, H2B, H3, and H4 come together to form a nucleosome. DNA is wrapped around the outside of the protein octamer with a stretch of DNA called the linker DNA that connects the nucleosomes to each other. The tails of the core histones can be observed in this figure. This basic structure is approximately 11 nm in diameter. 

DNA Wrapping:

  • Around 146 base pairs (bp) of DNA wrap 1.65 times around the histone octamer.
  • DNA is held tightly around histones by electrostatic interactions.

The position of the H1 histone on the nucleosome. 

Functions

DNA Packaging:

  • Compresses DNA, reducing its length to fit inside the nucleus.

Gene Regulation:

  • Controls access to DNA by transcription machinery.
  • Tight packaging prevents transcription (heterochromatin), while looser packaging allows transcription (euchromatin).

Higher-Order Organization

Beads-on-a-String Model:

  • Nucleosomes appear as “beads” connected by linker DNA (“string”) under low compaction.

DNA in the interphase nucleus is organized and packaged. First, the DNA is wrapped around core histones to form nucleosomes. H1 then helps loop nucleosomes together into a fiber, which then can be further looped and packaged inside the nucleus in a highly organized manner. 

Schematic showing structural elements found in a typical chromosome. Every chromosome contains structural elements such as the telomere and centromere that remain packaged into heterochromatin. In addition, genetic regions can be either loosely packed as euchromatin or more densely packed as heterochromatin. 

Clinical Relevance

Epigenetics:

  • Nucleosome positioning and histone modifications play key roles in regulating gene expression without altering the DNA sequence.

Cancer:

  • Altered nucleosome positioning or histone modifications can lead to uncontrolled cell growth.

Chromosomal Disorders:

  • Improper chromatin compaction may lead to genomic instability, contributing to diseases.

Important Features for Cell Division:

  • Centromeres:
    • Critical in mitosis for proper chromatid separation (discussed in later sections).
  • Telomeres:
    • Protect chromosome ends and prevent genetic loss during replication (further discussed in upcoming sections).

Practise Questions

Quizes

Table of Contents