The document discusses various aspects of genome organization, including: 1. Chromatin assembly begins with the incorporation of histone proteins to form nucleosomes, which are then folded and organized into higher order structures within the nucleus. 2. Genes can be split, overlapping, or pseudogenes. Split genes contain introns that are spliced out, while overlapping genes share nucleotide sequences. Pseudogenes are non-functional copies of genes. 3. Gene families consist of genes related by common ancestry that may be clustered or dispersed throughout the genome. Members can vary in sequence but often retain similar functions.

1. Genome Organization
Dr. M. Sonia Angeline
KJC

2. General steps
in chromatin
assembly
The assembly of DNA into chromatin involves a range of events, beginning with the
formation of the basic unit, the nucleosome, and ultimately giving rise to a complex
organization of specific domains within the nucleus.
The first step is the deposition onto the DNA of a tetramer of newly synthesized (H3-
H4)2 to form a sub-nucleosomal particle, which is followed by the addition of two
H2A-H2B dimers.
This produces a nucleosomal core particle consisting of 146 base pairs of DNA
wound around the histone octamer.
This core particle and the linker DNA together form the nucleosome.
Newly synthesized histones are specifically modified (e.g.the acetylation of histone
H4).

3. General steps
in chromatin
assembly
The next step is the maturation step that requires ATP to establish regular spacing of
the nucleosome cores to form the nucleofilament.
During this step the newly incorporated histones are de-acetylated.
Next the incorporation of linker histones is accompanied by folding of the
nucleofilament into the 30nm fibre, the structure of which remains to be elucidated.
Two principal models exist : the solenoid model and the zig zag.
Finally, further successive folding events lead to a high level of organization and
specific domains in the nucleus.
At each of the steps described above, variation in the composition and activity of
chromatin can be obtained by modifying its basic constituents and the activity of
stimulatory factors implicated in the processes
of its assembly and disassembly.

4. Assembly begins with the incorporation of the H3/H4 tetramer (1),
followed by the addition of two H2A-H2B dimers (2) to form a core particle. The
newly synthesized histones utilized are specifically modified; typically, histone H4 is
acetylated at Lys5 and Lys12 (H3-H4*).
Maturation requires ATP to establish a regular spacing, and histones are de-acetylated
(3).
The incorporation of linker histones is accompanied by folding of the nucleofilament.
Here the model presents a solenoid structure in which there are six nucleosomes per
gyre (4).
Further folding events lead ultimately to a defined domain organization within the
nucleus (5).

5. FUNCTIONOF
CHROMATIN
 The function of the chromatin is to carry out the genetic
information from one generation to another, by encoding
the past history and future prospects of the cell.
 DNA, being the only permanent component of chromatin,
is the sole genetic material of eukaryotes.
 It never leaves the cell, thus maintaining heredity of the
cell
 DNA is the permanent component of chromosomes and is
the sole genetic material of eukaryotes

6. Split,
Overlapping &
Pseudogenes
Split genes are the sequences containing actual information
of the gene (exons) are interrupted by other
sequences (introns) which are spliced out after transcription;
Overlapping gene sare same as DNA sequences can become
part of two or more genes expressed at different times and in
different reading frames.
Pseudogenes, which represent DNA sequences derived from
mRNA through reverse transcription; these pseudogenes,
therefore, differ from the split genes to which they belong, due
to the absence of intron sequences.

7. Split genes or
Interrupted
Genes:
 The coding regions containing actual information of the genes
(exons) of most eukaryotic genes are interrupted by few to several
noncoding sequences called introns (from intervening sequences)
which are spliced out after transcription
 Such genes are called split genes since their coding sequences are
split into several parts due to the introns.
 But some genes of eukaryotes are not split, e.g., histone genes of
sea urchin.
 The first split gene to be described in 1977 by Pierre Chambon and
his colleagues was the ovalbumin genes of chicken coding for the
386 amino acid long ovalbumin protein of eggs.

8. Split genes or
Interrupted
Genes:

9. Important
features of
interrupted
genes:
 1. Each interrupted gene begins’ with an exon and ends with an
exon.
 2.The exons occur in the same precise order in the mRNA in which
they occur in the gene.
 3.The same interrupted gene organisation is consistently present
in all the tissues of organisms.
 4. Most introns are blocked in all reading frames i.e., termination
codons occur frequently in their three reading frames.Therefore,
most introns do not seem to have coding functions.

10. Significance
ofSplitGenes:
 The significance of split organisation of eukaryotic genes is not
clear.
 1. In some cases, different exons of a gene code for different
active regions of the protein molecule, e.g., in the case of
antibodies.Thus, it has been suggested that introns are relics of
evolutionary processes that brought together different ancestral
genes to form new larger genes. It is also possible that some
introns have been introduced within certain exons during
evolution.
 2. Introns may also provide for increased recombination rates
between exons of a gene and thus may be of some significance in
genetic variation.
 3. Introns are known to code for enzymes involved in the
processing of hn RNA (heterogenous RNA).

11. Overlapping
Genes:
 The determination of nucleotide sequences of some viral genomes
such as bacteriophage (ɸx174 has clearly shown that at least some
genes share their nucleotide sequences either partially or fully; such
genes are called overlapping genes.
 Overlapping genes have been found in the following viruses; MS2
(single stranded RNA), SV40 (double stranded DNA) and phage k
(double stranded DNA).
 It has also been discovered in tryptophan mRNA of E. coli.
 In view of wide occurrence of overlapping genes, it seems that this
phenomenon is an economic device to make better use of genetic
material through packing of more genetic information in lets DNA.
 It is not known if overlapping genes occur in other prokaryotes and in
eukaryotes, or if they are confined to viruses.
 Overlapping genes cannot undergo mutation in’ independent of each
other, i.e., they will mutate together, although degeneracy of code
may permit some degree of independence.
 Therefore, a single mutation in the overlapping region of such genes
would often result in the loss of activities of two gene products, thus
generating pleiotropy.

12. Pseudogenes:
 In multicellular organisms, a wide variety of DNA sequences are
found, which are of no apparent use.
 Some of these sequences are defective copies of functional genes
and are, therefore called pseudogenes.
 Their general organisation is similar to those of interrupted genes
as they have sequences corresponding to introns and exons.
 They are non-functional due to mutations which prevent one or
more, often more of the following: transcription, RNA splicing and
translation (due to frequent occurrence of termination codons).
 The pseudogenes are common features of gene clusters and occur
with their functional counterparts.
 These pseudogenes have been reported in human beings, mouse
and Drosophila.

13. The most
popular
examples of
these
pseudogenes
include the
following.
 (i) Human α-globin and β-globin pseudogenes (Ψ) found in each of the
two globin clusters.
 (ii) In mouse there are few a-globin pseudogenes (Ψ), one of them
(Ψα3) is different from other pseudogenes since it has no introns
which are present in a-globin genes as well as in other pseudogenes.
 (iii) UsnRNA series of pseudogenes in human beings includes
U1 U2 and U3sn RNA pseudogenes.
 (iv) In Drosophila histone pseudogenes have been discovered.,
 Several pseudogenes lack introns and resemble mature mRNA
transcripts of their active counterparts, they are called processed
pseudogenes.
 These pseudogenes are believed to be reverse transcripts of mature
mRNAs which become inserted into the genome.
 Such genes are flanked by direct repeats of 6-21 bp and are located
anywhere in the genome irrespective of the location of the concerned
functional genes.
 For example, the mouseTa 3 globin gene in mouse.

14. Gene
Families:
 A gene family consists of all those genes that have related sequences
and are believed to have originated form a common ancestral gene
through gene duplication and subsequent mutational variation.
 The members of a gene family may be clustered together or dispersed
on different chromosomes.
 Some gene families consists of identical members; such genes always
occur in clusters and have two (on lower extreme) to hundreds of
identical genes in tandem.
 Extensive tandem repetition of a gene normally occurs when the gene
product is needed in unusually large amounts, e.g., genes for rRNA,
histone genes etc.
 The members of a gene family usually have related functions.
 When related genes occur at several locations, they are believed to
have arisen through translocation of members located in a cluster.
 The genes usually become divergent after they become dispersed.
 Sometimes all the members of a gene family are functional, but often
some members are nonfunctional pseudogenes.