DNA Ekstrakromosomal,

Sifat, dan Kegunaannya

Soraya Rahmanisa

Pengertian
DNA ekstrakromosomal : DNA

lain yang terdapat dalam sel di

luar nukleus, yaitu :
- DNA mitokondria, DNA
kloroplas, DNA plasmid

TheGenomeDefines the Program of Multicellular

Development
Thecellsin an individual animal or plant are extraordinarily varied. Fatcells,
skincells, bonecells, nervecellsthey seem as dissimilar as anycellscould
be. Yet all these cell types are generated during embryonic development from
a single fertilized egg cell, and all (with minor exceptions) contain identical
copies of thegenomeof the species.
The explanation lies in the way in which thesecellsmake selective use of their
genetic instructions according to the cues they get from their surroundings.
The DNA is not just a shopping list specifying the molecules that every cell
must have, and the cell is not an assembly of all the items on the list. Rather,
the cell behaves as a multipurpose machine, with sensors to receive
environmental signals and highly developed abilities to call different sets of
genes into action according to the sequences of signals to which the cell has
been exposed. A large fraction of the genes in the eucaryoticgenomecode for
proteins that serve to regulate the activities of other genes. Most of thesegene
regulatory proteinsact by binding, directly or indirectly, to the regulatory DNA
adjacent to the genes that are to be controlled (Figure 1-40), or by interfering
with the abilities of other proteins to do so. The expandedgenomeof
eucaryotes therefore serves not only to specify the hardware of the cell, but
also to store the software that controls how that hardware is used.

EucaryoticGenomesAre Rich in Regulatory

DNA

Much of our noncoding DNA is almost certainly

dispensable junk, retained like a mass of old papers
because, when there is little pressure to keep an
archive small, it is easier to retain everything than
to sort out the valuable information and discard the
rest. Certain exceptional eucaryotic species, such
as the puffer fish (Figure 1-39), bear witness to the
profligacy of their relatives; they have somehow
managed either to rid themselves of large
quantities of noncoding DNA, or to have avoided
acquiring it in the first place. Yet they appear
similar in structure, behavior, and fitness to related
species that have vastly more such DNA.

DNA
- inheritance blueprint
- consist the genes (functional units)
- covered into chromosome
Chromosomal aberration
include the genes (multi genes)

Chromosome Abnormalities

The puffer fish(Fugu rubripes).. This

organism has agenomesize of 400 million

nucleotide pairsabout one-quarter as
much as a zebrafish, for example, even
though the two species of fish have similar
numbers of genes. (From a woodcut by
Hiroshige,

Even in compact eucaryoticgenomessuch as

that of puffer fish, there is more noncoding
DNA than coding DNA, and at least some of
the noncoding DNA certainly has important
functions. In particular, it serves to regulate
the expression of adjacent genes. With this
regulatory DNA, eucaryotes have evolved
distinctive ways of controlling when and
where a gene is brought into play. This
sophisticated gene regulation is crucial for the
formation of complex multicellular organisms.

In a developing multicellular organism, each cell is

governed by the same control system, but with
different consequences depending on the
signals the cell exchanges with its neighbors.
The outcome, astonishingly, is a precisely
patterned array ofcellsin different states, each
displaying a character appropriate to its position
in the multicellular structure. Thegenomein
each cell is big enough to accommodate the
information that specifies an entire multicellular
organism, but in any individual cell only part of
that information is used

The Mouse Serves as a Model for Mammals

Mammals have typically three or four times as many genes

asDrosophila,agenomethat is 20 times larger, and millions or billions of

times as manycellsin their adult bodies. In terms ofgenomesize and
function, cell biology, and molecular mechanisms, mammals are nevertheless
a highly uniform group of organisms. Even anatomically, the differences
among mammals are chiefly a matter of size and proportions; it is hard to
think of a human body part that does not have a counterpart in elephants and
mice, and vice versa. Evolution plays freely with quantitative features, but it
does not readily change the logic of the structure.
To get a more exact measure of how closely mammalian species resemble
one another genetically, we can compare the nucleotide sequences of
corresponding (orthologous) genes, or the amino acid sequences of the
proteins that these genes encode. The results for individual genes and
proteins vary widely. But typically, if we line up the amino acid sequence of a
human protein with that of the orthologous protein from, say, an elephant,
about 85% of the amino acids are identical. A similar comparison between
human and bird shows an amino acid identity of about 70%twice as many
differences, because the bird and the mammalian lineages have had twice as
long to diverge as those of the elephant and the human

Human and mouse:

similar genes and
similar development.
The human baby and
the mouse shown
here have similar
white patches on their
foreheads because
both have mutations
in the same gene
(calledkit),required
for the development
and maintenance of
pigment
Source : Molecular
Biology of the Cell.
4th edition.
Alberts B, Johnson A,
Lewis J, et al.
New York:
Garland Science;
2002.

Eucaryoticcells, by definition, keep their DNA in a separate membrane-bounded

compartment, the nucleus. They have, in addition, a cytoskeleton for movement, elaborate
intracellular compartments for digestion and secretion, the capacity (in many species) to
engulf othercells, and a metabolism that depends on the oxidation of organic molecules by
mitochondria. These properties suggest that eucaryotes originated as predators on othercells.
Mitochondriaand, in plants, chloroplastscontain their own genetic material, and evidently
evolved from bacteria that were taken up into the cytoplasm of the eucaryotic cell and
survived as symbionts. Eucaryoticcellshave typically 330 times as many genes as
procaryotes, and often thousands of times more noncoding DNA. The noncoding DNA allows for
complex regulation of gene expression, as required for the construction of complex
multicellular organisms. Many eucaryotes are, however, unicellular, among them the
yeastSaccharomyces cerevisiae, which serves as a simple model organism for eucaryotic cell
biology, revealing the molecular basis of conserved fundamental processes such as the
eucaryotic cell division cycle. A small number of other organisms have been chosen as primary
models for multicellular plants and animals, and the sequencing of their entiregenomeshas
opened the way to systematic and comprehensive analysis of gene functions, gene regulation,
and genetic diversity. As a result of gene duplications during vertebrate evolution,
vertebrategenomescontain multiple closely related homologs of most genes. This genetic
redundancy has allowed diversification and specialization of genes for new purposes, but it
also makes gene functions harder to decipher. There is less genetic redundancy in the
nematodeCaenorhabditis elegansand the flyDrosophila melanogaster, which have thus
played a key part in revealing universal genetic mechanisms of animal development.

In eucaryotes, theDNAin thenucleusis divided between a set of differentchromosomes . For example,

Eucaryotic
DNA Is Packaged
into a Set
of over
Chromosomes
the humangenomeapproximately
3.2 10 nucleotidesis
distributed
24 different

chromosomes. Eachchromosome consists of a single, enormously long linear DNAmoleculeassociated

with proteins that fold and pack the fine DNA thread into a more compact structure. Thecomplexof
DNA andproteinis calledchromatin(from the Greekchroma, color, because of its staining
properties). In addition to the proteins involved in packaging the DNA, chromosomes are also
associated with many proteins required for the processes ofgeneexpression, DNA replication, and
DNA repair.
Bacteria carry their genes on a singleDNAmolecule, which is usually circular (seeFigure 1-30). This
DNA is associated with proteins that package and condense the DNA, but they are different from the
proteins that perform these functions in eucaryotes. Although often called the bacterial chromosome
, it does not have the same structure as eucaryotic chromosomes, and less is known about how the
bacterial DNA is packaged. Even less is known about how DNA is compacted in archaea. Therefore, our
discussion of chromosome structure will focus almost entirely on eucaryotic chromosomes.
With the exception of the germcells, and a few highly specialized cell types that cannot multiply and
lackDNAaltogether (for example, red bloodcells), each human cell contains two copies of each
chromosome , one inherited from the mother and one from the father. The maternal and paternal
chromosomes of a pair are calledhomologouschromosomes (homologs). The only nonhomologous
chromosome pairs are the sex chromosomes in males, where aY chromosomeis inherited from the
father and anX chromosomefrom the mother. Thus, each human cell contains a total of 46
chromosomes22 pairs common to both males and females, plus two so-called sex chromosomes (X
and Y in males, two Xs in females).DNAhybridization(described in detail in Chapter 8) can be used to
distinguish these human chromosomes by painting each one a different color (Figure 4-10).
Chromosome painting is typically done at the stage in the cell cycle when chromosomes are especially
compacted and easy to visualize

Nucleosomes Are the Basic Unit of Eucaryotic

Chromosome Structure
The proteins that bind to theDNAto form eucaryotic chromosomes are

traditionally divided into two general classes: thehistonesand

thenonhistone chromosomal proteins. Thecomplexof both classes of
proteinwith the nuclear DNA of eucaryoticcellsis known aschromatin.
Histones are present in such enormous quantities in the cell (about 60
million molecules of each type per human cell) that their total mass in
chromatinis about equal to that of the DNA.
Histones are responsible for the first and mostbasiclevel ofchromosome
organization, thenucleosome, which was discovered in 1974. When
interphasenuclei are broken open very gently and their contents
examined under theelectron microscope, most of thechromatinis in the
form of a fiber with a diameter of about 30nm(Figure 4-23A). If this
chromatin is subjected to treatments that cause it to unfold partially, it
can be seen under the electron microscope as a series of beads on a
string (Figure 4-23B). The string isDNA, and each bead is a nucleosome
core particle that consists of DNA wound around aproteincore formed
from histones. The beads on a string represent the first level of
chromosomal DNA packing.

Structural
organization of
the
nucleosome. A
nucleosome
contains a
protein core
made of eight
histone
molecules. As
indicated, the
nucleosome
core particle is
released from
chromatin by
digestion of
the linker DNA
with a
nuclease, an
enzyme that
breaks

Eachnucleosomecore particle is separated from the

next by a region of linkerDNA, which can vary in
length from a fewnucleotidepairs up to about 80. (The
termnucleosometechnically refers to a nucleosome
core particle plus one of its adjacent DNA linkers, but it
is often used synonymously with nucleosome core
particle.) On average, therefore, nucleosomes repeat
at intervals of about 200 nucleotide pairs. For example,
adiploidhuman cell with 6.4 109nucleotide pairs
contains approximately 30 million nucleosomes. The
formation of nucleosomes converts a DNAmolecule
into achromatinthread about one-third of its initial
length, and this provides the first level of DNA packing.

TheStructureofDNAProvides a Mechanism for

Heredity

Genes carry biological information that must be copied accurately for transmission to the next generation

each time a cell divides to form two daughter cells. Two central biological questions arise from these
requirements: how can the information for specifying an organism be carried in chemical form, and how is
it accurately copied? The discovery of thestructureof theDNAdouble helixwas a landmark in
twentieth-century biology because it immediately suggested answers to both questions, thereby resolving
at the molecular level the problem of heredity. We discuss briefly the answers to these questions in this
section, and we shall examine them in more detail in subsequent chapters.
DNAencodes information through the order, or sequence, of the nucleotides along each strand. Eachbase
A, C, T, orGcan be considered as a letter in a four-letter alphabet that spells out biological messages
in the chemicalstructureof theDNA. As we saw in Chapter 1, organisms differ from one another
because their respectiveDNAmolecules have differentnucleotidesequences and, consequently, carry
different biological messages. But how is the nucleotide alphabet used to make messages, and what do
they spell out?
As discussed above, it was known well before thestructureofDNAwasdeterminedthat genes contain
the instructions for producing proteins. TheDNAmessages must therefore somehow encode proteins (
Figure 4-6). This relationship immediately makes the problem easier to understand, because of the
chemical character of proteins. As discussed in Chapter 3, the properties of aprotein, which are
responsible for its biologicalfunction, are determined by its three-dimensionalstructure, and
itsstructureis determined in turn by the linear sequence of the amino acids of which it is composed. The
linear sequence of nucleotides in agenemust therefore somehow spell out the linear sequence of amino
acids in a protein. The exact correspondence between the four-letternucleotidealphabet ofDNAand the
twenty-letteramino acidalphabet of proteinsthegenetic codeis not obvious from theDNAstructure,
and it took over a decade after the discovery of thedouble helixbefore it was worked out. In Chapter 6 we
describe this code in detail in the course of elaborating the process, known asgeneexpression, through
which a cell translates the nucleotide sequence of a gene into the amino acid sequence of a protein.

The complete set of information in an organism'sDNAis

called itsgenome, and it carries the information for all
the proteins the organism will ever synthesize. (The term
genomeis also used to describe theDNAthat carries this
information.) The amount of information contained in
genomes is staggering: for example, a typical human cell
contains 2 meters ofDNA. Written out in the four-letter
nucleotidealphabet, the nucleotide sequence of a very
small humangeneoccupies a quarter of a page of text (
Figure 4-7), while the complete sequence of nucleotides
in the human genome would fill more than a thousand
books the size of this one. In addition to other critical
information, it carries the instructions for about 30,000
distinct proteins.

In Eucaryotes,DNAIs Enclosed in a Cell

Nucleus
Nearly all theDNAin a eucaryotic cell is sequestered in

anucleus, which occupies about 10% of the total cell

volume. Thiscompartmentis delimited by a
nuclear envelopeformed by two concentriclipid bilayer
membranes that are punctured at intervals by large
nuclear pores, which transport molecules between the
nucleus and thecytosol. The nuclear envelope is
directly connected to the extensive membranes of the
endoplasmic reticulum. It is mechanically supported by
two networks of intermediate filaments: one, called
thenuclear lamina, forms a thin sheetlike meshwork
inside the nucleus, just beneath the
inner nuclear membrane; the other surrounds theouter
nuclear membraneand is less regularly organized