chp11

Abbreviations for D/RNA Length

• bp = base pair

  • One base pair corresponds to approximately 3.4 Å (340 pm) of length along the strand.

• kb (kbp) = kilo–base-pair = 1,000 bp

• Mb (Mbp) = mega–base-pair = 1,000,000 bp

• Gb (Gbp) = giga–base-pair = 1,000,000,000 bp

Chromosome Structure

Bacteriophage T2

• An electron micrograph shows the bacteriophage T2 with DNA released by osmotic shock.

• The chromosome is approximately 52 µM long and is ~170 Kbp.

Overview of Chromosomes

• Most chromosomes are composed of DNA and proteins.

Viral and Bacterial Chromosomes

Characteristics

• Viral and bacterial chromosomes are:

  • Single nucleic acid molecules.

  • Largely devoid of associated proteins.

  • Much smaller than eukaryotic chromosomes.

  • Contain less genetic information.

Table of Genetic Material of Representative Viruses and Bacteria

Distinctions of Bacterial and Viral Genomes

• Bacterial genomes are double-stranded DNA, while viral genomes can be RNA or DNA, with some viruses being single-stranded and others double-stranded.

Bacterial Chromosomes

Structure

• Circular, double-stranded DNA compacted into a nucleoid.

• DNA Binding Proteins:

  • HU and H-NS (Histone-like Nucleoid Structuring Protein) facilitate folding and bending of DNA, creating coils for compaction.

Key Features

• Bacterial chromosomes typically:

  • Are circular.

  • Usually contain a few million base pairs.

  • Have a single type of chromosome, but may be present in multiple copies.

  • Contain several thousand different genes interspersed throughout.

  • Have intergenic regions, which are the regions between adjacent genes.

  • Require one origin of replication to initiate DNA replication.

  • May contain repetitive sequences interspersed within the chromosome.

Location and Structure of Bacterial Chromosomes

• Bacterial chromosomes are located in a region called the nucleoid, which is not surrounded by a membrane.

Mitochondria and Chloroplasts

• Mitochondria and chloroplasts contain their own DNA, which is inherited through maternal cytoplasm in most organisms.

• Their DNA is remarkably similar to that of viruses and bacteria.

Organization of Eukaryotic Chromosomes

Key Components

• Eukaryotic chromosomes are composed of long, linear DNA molecules, and three types of DNA sequences are required for chromosomal replication and segregation:

  • Origins of replication

  • Centromeres

  • Telomeres

Characteristics of Eukaryotic Chromosomes

• Length can range from tens of millions to hundreds of millions of bp.

• Occur in sets.

• Genes are interspersed throughout the chromosome.

• Each chromosome contains multiple origins of replication, about every 100,000 base pairs.

• Has a centromere that forms a recognition site for kinetochore proteins.

• Contains telomeres, which are specialized sequences located at the ends of linear chromosomes.

• Repetitive sequences are typically found near centromeric and telomeric regions but may also be interspersed.

Comparison Between Eukaryotic and Prokaryotic Chromosomes

• Eukaryotic chromosomes exhibit distinctions such as size, complexity, and arrangement of genetic material in comparison to prokaryotic chromosomes.

Genome Sizes Among Eukaryotes

• Genome sizes differ significantly among various groups of organisms, with haploid genome sizes (nucleotide base pairs) ranging from 10^6 to 10^12.

Classes of DNA Sequences in the Human Genome

• The human genome consists of percentages distributed among regions of genes that encode proteins (exons), introns, unique noncoding DNA, and repetitive DNA:

  • Exons: 2%

  • Introns and other parts of genes: 24%

  • Unique noncoding DNA: 15%

  • Repetitive DNA: 59%

Types of Repetitive DNA

Overview

• The categories of repetitive DNA include:

  • Highly repetitive DNA

  • Middle repetitive DNA

  • Satellite DNA

  • Tandem repeats

  • Interspersed retrotransposons

  • Multiple-copy genes

  • Mini-satellites

  • Micro-satellites

  • SINEs and LINEs

  • rRNA genes

  • VNTRs and STRs

  • Alu and L1 sequences

Eukaryotic Chromatin Compaction

Importance of Compaction

• DNA must be tightly compacted to fit within the nucleus, involving interactions between DNA and various proteins, forming a DNA-protein complex known as chromatin.

Nucleosome Structure

• The basic subunit of chromatin is the nucleosome, proposed by Roger Kornberg in 1974.

• A nucleosome consists of double-stranded DNA wrapped around an octamer of histone proteins.

  • Histone Octamer Composition:

  • Two copies each of four different histones: H2A, H2B, H3, and H4.

  • Histones contain many positively-charged amino acids.

• 146 bp of DNA make approximately 1.65 negative superhelical turns around the octamer.

Structure of Nucleosomes

• Nucleosomes appear like “beads on a string” along chromatin strands derived from Drosophila melanogaster.

• The connected structure of nucleosomes shortens the DNA length approximately seven-fold.

30-nm Fiber Structure

• Nucleosomes associate to form a compact structure known as the 30-nm fiber.

• This further shortens the total length of DNA about 50-fold and involves interactions between the 30-nm fiber and the nuclear matrix.

Nuclear Matrix

Composition

• The nuclear matrix consists of two parts:

  • Nuclear lamina: Fibers lining the inner membrane.

  • Internal nuclear matrix: Connects to the lamina, filling the nucleus interior.

Function

• The nuclear matrix compacts DNA into radial loop domains.

• Matrix-Attachment Regions (MARs) are DNA sequences that anchor to the nuclear matrix, creating radial loops ranging from 25,000 to 200,000 bp.

Chromatin Types: Euchromatin and Heterochromatin

Euchromatin

• Less condensed regions of chromosomes, transcriptionally active, areas where the 30-nm fiber forms radial loop domains.

Heterochromatin

• Tightly compacted regions of chromosomes, generally transcriptionally inactive, where radial loop domains are compacted even further.

Metaphase Chromosomes and Compaction Changes

• As cells enter M phase, the level of chromatin compaction changes dramatically, and by the end of prophase, sister chromatids become entirely heterochromatic.

Comparison of Chromatin Packaging Levels

• The most tightly packed chromatin levels in order are:

  1. Naked DNA

  2. DNA packaged in nucleosomes

  3. Metaphase chromosomes

  4. 30nm fiber

Modifications of Chromatin Packaging

• Chromatin packaging can be altered through:

  • Chromatin remodeling

  • Chemical modifications on histone tails:

  • Acetylation

  • Methylation

  • Phosphorylation

  • DNA methylation:

  • 5-methyl cytosine