Untitled Notes

Chromosomes in eukaryotes consist of: - A single molecule of DNA. - Associated with: - Many copies of five kinds of histones. - A small number of copies of various non-histone proteins. - Many non-histone proteins are transcription factors regulating RNA transcription. - Others regulate DNA replication, repair, and recombination.

Most of the time, chromosomes are too elongated and tenuous to be visible under a microscope.
Before cell division by mitosis: - Each chromosome is duplicated during the S phase of the cell cycle.
As mitosis begins: - Duplicated chromosomes condense into short (~5 µm) structures. - Staining allows for easy observation under a light microscope.

Cell cycle phases include: - Interphase: Early Growth Stages - G₁ phase: Primary growth phase. - S phase: DNA replication occurs here. - G₂ phase: Microtubule synthesis prepares for mitosis. - Mitosis (M phase): Chromosomes are pulled apart. - Cytokinesis (C phase): Division of the cytoplasm occurs.

Duplicated chromosomes, called dyads, are held together at the centromere.
In humans, the centromere contains over 3 million base pairs of DNA: - Primarily composed of repetitive DNA consisting of short sequences (e.g., 171 bp) that repeat in tandem arrays.
Kinetochore: A protein complex that forms at the centromere. - Aids separation of sister chromatids during anaphase.
Staining with the trypsin-Giemsa method reveals: - Alternating light and dark bands called G bands. - G bands are numerically indexed providing "addresses" for gene loci assignments.

Chromosomes labeled with various banding patterns.
Key regions include: - Telomeres: Repetitive sequences at the ends of chromosomes. - Centromeres: Constricted regions of chromosomes, critical for segregation during mitosis.

A karyotype is the complete set of chromosomes in the cells of an organism.
Dyads found in homologous pairs: - One from each parent, showcasing characteristic diploid (2n) number for species.
Examples: - Human female karyotype: 23 pairs (22 autosomes + 1 pair of X chromosomes). - Human male karyotype: 23 pairs (22 autosomes + 1 X + 1 Y chromosomes; sex chromosomes).

During interphase, chromatin structure is not clearly visible, but density varies: - Heterochromatin: - Dense, transcriptionally inactive, found near centromeres and telomeres. - Seen as dense patches of chromatin, often lining nuclear membrane but broken by clear pores for transport. - Euchromatin: - Less dense, contains many genes, and is associated with active transcription in cells. - Loosely packed in loops of 30 nm fibers, separated by insulators.

Chromosome mapping confirms that active genes largely reside in euchromatin: - Euchromatin stains lighter due to its less compact structure. - Ratio of Drosophila heterochromatin mapping to genes is only 1/100 compared to euchromatin.

Size of DNA in human chromosomes ranges: - Smallest chromosome: $50 imes 10^6$ nucleotide pairs (stretch ~? cm). - Largest chromosome: $250 imes 10^6$ nucleotide pairs (stretch ~? cm).
Each nucleus contains $6 imes 10^9$ base pairs of DNA: - Totaling about ? m of DNA per chromosome set.
Human body has approximately $10^{13}$ cells, leading to about ? x $10^{13}$ m of total DNA.

The DNA must be compacted to fit within the cell nucleus, defined by its packing ratio.
DNA-protein complex (chromatin) is highly organized to allow storage within the nucleus.
The fundamental unit of chromatin is the nucleosome: - DNA is wound around a protein core to create a bead-like structure. - This structure exists in both euchromatin and heterochromatin.

Histones are positively charged proteins (rich in lysine and arginine). - Bind tightly to negatively charged DNA phosphates. - Present in quantities comparable to DNA within eukaryotic cells, suggesting evolutionary conservation of histone genes.

Nucleosome Formation: - Simplest structure found in all eukaryotic chromosomes where DNA wraps around an octamer of histone proteins. - Approximately 146 bp of DNA wraps around histone octamer (core histones: H2A, H2B, H3, H4). - The total packaged DNA is roughly 200 bp, leading to negative supercoiling.
30 nm Fiber Organization: - Coiling of nucleosomes into helical structures results in tighter packing (40 times reduction in length). - Histone H1 is critical for stabilization of this fiber structure.
Final Packaging Levels: - The final structure achieved is a 700 nm chromatin seen in metaphase chromosomes, resulting from extensive DNA looping and scaffolding.

Chromosomal DNA consists of: - Functional repetitive sequences (gene families, tandem arrays, noncoding functional sequences). - Sequences with no known functions (satellite DNA, variable number tandem repeats, and transposed sequences).

Dispersed Gene Families: - Families of homologous genes spread throughout the genome (e.g., actins with 20 members, keratins with >20).
Tandem Gene Family Arrays: - Large amounts of product required by cells lead to the evolution of tandem arrays (e.g., rRNA genes).
Noncoding Functional Sequences: - Chromosome tips with simple DNA sequences that do not encode products but have specific functions.

Highly Repetitive Centromeric DNA: - Satellite DNA forms repeats of short sequences in heterochromatic regions.
Variable Number Tandem Repeats (VNTRs): - Mini- and microsatellites consisting of repeating units of 15-10 nucleotides.
Transposed Sequences: - Repetitive elements that replicate and migrate throughout the genome (e.g., LINEs and SINEs).

Refers to remaining sections of DNA after functional units have been categorized.
Presumed function is to separate functional DNA units.