NUCLEOSOMES, SOLENOID

Reena Singh Chopra BTY 107

CHROMATIN LOOPS, CHROMATIN

Chromatin is a complex of macromolecules

found in cells, consisting of DNA, protein and

RNA.The primary functions of chromatin are 1) to

package DNA into a smaller volume to fit in the

cell, 2) to reinforce the DNA macromolecule to

allow mitosis, 3) to prevent DNA damage,

and 4) to control gene expression and DNA

replication.

Forms of Chromatin:

Euchromatin is a lightly packed form of

chromatin (DNA, RNA and protein)

Euchromatin comprises the most active portion

of the genome within the cell nucleus. 92% of the

human genome is euchromatic.

Heterochromatin is a tightly packed form of DNA, which comes in multiple

varieties.

Histones: Basic proteins. Play a major role in chromatin. They are present in the

chromatin of all eukaryotes in amounts equivalent to the amounts of DNA .

The major five histones are known as H1, H2A,H2B,H3 and H4. The molar ratio of

histones are 1H1, 2HA,2HB,2H3 and 2H4.

Composition of Histones

In eukaryotes, the DNA-protein complex, called chromatin is ordered into

higher structural levels than the DNA-protein complex in prokaryotes

Eukaryotic DNA

Is precisely combined with a large amount of

protein

Eukaryotic chromosomes

Contain an enormous amount of DNA

relative to their condensed length

Proteins called histones are responsible for the first level of DNA packing in

chromatin and bind tightly to DNA

The association of DNA and histones seems to remain intact throughout the cell

cycle

Nucleosomes: The histones specifically complexed with DNA to produce the basic structural

subunits of chromatin, small(approx. 110 Ao in diameter) ellipsoidal “beads”called nucleosomes.

Solenoid: The nucleosomes, and the DNA strands linking them, are packed closely together to

produce a 30nm diameter helix with about six nucleosome per turn. This is known as the 30nm

fibre, or the solenoid fibre.

It has a packing ratio of about 440, that 40um of DNA are packed into 1um length of

solenoid.

In electron micrographs

Unfolded chromatin has the appearance of beads on a string

Each “bead” is a nucleosome: The basic unit of DNA packing

Nucleosomes (10-nm fiber)

The next level of packing forms the 30-nm chromatin fiber

Nucleosome

30 nm

30-nm fiber

The 30-nm fiber, in turn forms looped domains, making up a 300-nm fiber

Protein scaffold

300 nm

Looped domains (300-nm fiber)

Loops

Scaffold

In a mitotic chromosome the looped domains themselves coil and fold forming

the characteristic metaphase chromosome

700 nm

1,400 nm

Metaphase chromosome

In interphase cells most chromatin is in the highly extended form called euchromatin

VARIATION IN CHROMOSOME

STRUCTURE AND NUMBER

Chromosome Number in Different Species

In "higher” organisms (diploids), members of same species typically have

identical numbers of chromosomes in each somatic cell. Diploid

chromosome number (2n). Nearly all chromosomes will exist in pairs

(identical wrt length and centromere placement) except the sex

chromosome Y. Members of pair are homologous chromosomes. Haploid

number (n) is the number of chromosome pairs.

Amount of genetic information in the chromosome can change

Deficiencies/Deletions

Duplications

Variation In Chromosome Structure

Single Chromosome Disorders 1. Deletion

2. Genetic material

1.Deletion

• Genetic material is missing

2. Duplication

• Genetic material is present twice

• is present twice

3. Inversion

A chromosomal deficiency occurs when a

chromosome breaks and a fragment is lost

Deficiencies (aka Deletions)

Phenotypic consequences of deficiency depends on

Size of the deletion

Functions of the genes deleted

Phenotypic effect of deletions usually detrimental

Deficiencies

Cri-du-chat Syndrome

A chromosomal duplication is usually caused by

abnormal events during recombination

Duplications

Phenotypic consequences of duplications correlated to size & genes involved

Duplications tend to be less detrimental

Duplications

Bar-Eye Phenotype in Drosophila

• Phenotype: reduced number of ommatidia

• Ultra-bar (or double-bar) is a trait in which flies have even

fewer facets than the bar homozygote

• Both traits are X-linked and show intermediate dominance

Bar-eye Phenotype due to Duplication

Majority of small duplications have no phenotypic effect

However, they provide raw material for evolutionary change

Lead to the formation of gene families

A gene family consists of two or more genes that are

similar to each other

derived from a common gene ancestor

Well-studied example is the globin gene family

Genes encode proteins that bind oxygen

Duplications and Gene Families

Genes derived

from a single

ancestral gene

Duplications Generate Gene Families

A segment of chromosome that is flipped relative to

that in the homologue

Inversions

Centromere lies

within inverted

region

Centromere lies

outside inverted

region

Inversions

• No loss of genetic information

– Many inversions have no phenotypic consequences

• Break point effect

– Inversion break point is within regulatory or structural portion of a

gene

• Position effect

– Gene is repositioned in a way that alters its gene expression

– separated from regulatory sequences, placed next to constitutive

heterochromatin

• ~ 2% of the human population carries karyotypically

detectable inversions

Individuals with one copy of a normal chromosome and one

copy of an inverted chromosome

Usually phenotypically normal

Have a high probability of producing gametes that are abnormal in

genetic content

Abnormality due to crossing-over within the inversion interval

During meiosis I, homologous chromosomes synapse with

each other

For the normal and inversion chromosome to synapse properly, an

inversion loop must form

If a cross-over occurs within the inversion loop, highly abnormal

chromosomes are produced

Inversion Heterozygotes

Crossing Over Within Inversion Interval Generates Unequal Sets of Chromatids

Inversions Prevent Generation of Recombinant Offspring Genotypes

• Only parental chromosomes (non-recombinants) will produce normal progeny after fertilization

When a segment of one chromosome becomes

attached to another

In reciprocal translocations two non-homologous

chromosomes exchange genetic material

Usually generate so-called balanced translocations

Usually without phenotypic consequences

Although can result in position effect

Translocations

Fig. 8.13b(TE Art)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Nonhomologous chromosomes

Reciprocal translocation

1 1 7 7

Nonhomologous crossover

1 7

Crossover between nonhomologous chromosomes

Fig. 8.13a(TE Art)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

22

Environmental agent causes 2 chromosomes to break.

Reactive ends

22

2 2

DNA repair enzymes recognize broken ends and connect them.

Chromosomal breakage and DNA repair

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

In simple translocations the transfer of genetic

material occurs in only one direction

These are also called unbalanced translocations

Unbalanced translocations are associated with

phenotypic abnormalities or even lethality

Example: Familial Down Syndrome

In this condition, the majority of chromosome 21 is

attached to chromosome 14

8-42

VARIATION IN

CHROMOSOME NUMBER