Chromosomes and gene regulation

• DNA is just information - a “blueprint”

• No use unless you know the rules for using the information

• DNA is organised (in chromosomes)

• The expression of genes is regulated

• These 2 lectures cover these 2 issues

Giant chromosome from Drosophila

(From course textbook)

Human chromosomes• Human body cells have 46 chromosomes in

pairs:– 22 pairs of autosomes (numbered 1 to 22)– 2 X chromosomes (female) or X and Y (male)

• Germ cells (sperm and egg) have 23 chromosomes– 22 autosomes and a Y or an X

• Body cells are diploid and germ cells are haploid

Human karyotype(picture of chromosomes)drawn from a photograph of chromosomestaken through a high-power microscope.

Routine lab method.Used in hospitals.

DNA is packaged into chromosomes• Each human cell contains 2 metres of DNA

(3,000,000,000 bases in a haploid cell)

• Nucleus is 5 microns (0.005 mm) diameter

• DNA must be properly packaged, not just tangled up and stuffed into nucleus

• Packaging involves coiling and folding the DNA in specific ways

• Special proteins are associated with DNA - together called chromatin

Cell cycle

• Cell cycle is the means by which cells divide

• Stages:

1. Chromosome replication

2. Mitosis

3. Cell division

• Chromosomes are extended during interphase, but condensed and visible under microscope during metaphase

interphase metaphase interphase

chromosomes

Mitotic spindle

chromosomes

nucleus

1 2 3

Features of the chromosome

• Centromere is required to attach to spindle at mitosis, so chromosomes segregate into new cells

• Telomeres protect the ends of chromosomes

• Replication origins are where DNA replication starts

telomere

centromere

telomere

replication

mitosis

2 new cells

Mitoticspindle

Nucleosomes & chromatin

• Extended DNA under electron microscope looks like “beads on a string”

• The beads are DNA coiled around a core of proteins (histones). DNA and proteins together are chromatin

• Each of these structures is a nucleosome

• Nucleosomes are the basic type of organisation of DNA in a chromosome

Structure of nucleosomes

Beads-on-string chromatin

Digestion with nuclease enzyme

Single nucleosomes

Histone proteins (8 subunits)146 bp DNA fragments

Overall packaging of DNA

2 nm

11 nm

30 nm

300 nm

700 nm

1400 nm

(1 nm = 0.000001 mm)

DNA double helix

Nucleosomes

Fibre of packed nucleosomes

Extended form of chromosome

Condensed form of chromosome

Entire chromosome

Chromatin and gene activity

• Stained chromosomes show bands

• Bands are due to different forms of chromatin

• Euchromatin is where the active genes are

• Heterochromatin has no or few active genes, found near centromeres and telomeres

Gene activity affected by position

heterochromatineuchromatin

White eye gene

inversion

Chromosomes in nucleus

• During interphase chromosomes are organised within nucleus

• Individual chromosomes probably attached at points to wall of nucleus

• Part of chromosomes are in a region called nucleolus