When we hear about DNA we
immediately think of chromosomes
in the nuclei of most cells of plants
and animals. These chromosomes
carry the vast bulk of the genetic
information that an organism has
inherited from both parents. We
humans have 46 chromosomes in
each nucleus (except in our sex
cells) - i.e. 23 from our father and
23 from our mother. Thus, nuclear
inheritance passes on genetic
material from both parents.
itochondria are found in
the cytoplasm of every
cell - they are tiny
structures where respiration occurs
i.e. where the energy is released
from our food.
The number of mitochondria in
each cell varies (from hundreds to
thousands), as the more energy a
cell needs the more mitochondria
will be found in that cell. Muscle
cells have a large number of
mitochondria as lots of energy is
needed for muscle action and liver
cells, too, have thousands of
mitochondria
Mitochondria are
found in the cytoplasm of cells in
animals, plants and fungi.
M
Every mitochondrion contains some
DNA - a small amount (relative to the
amount of DNA in the nucleus) 16,569 base pairs or 39 genes. It is
called mitochondrial DNA (mtDNA).
These 39 genes code for some of the
enzymes and other materials (e.g.
RNA) that are required for the
process of respiration. So, mutations
in the mtDNA may lead to
mitochondrial disorders (see page 2).
The human mitochondrial genome
was fully sequenced in the 1990s. All
mtDNA is a double stranded circular
molecule, not unlike a plasmid in a
bacterial cell. Each mitochondrion
contains between two and ten
copies of this circular molecule. This
means that a cell with, for example, a
thousand mitochondria could have
ten thousand copies of the mtDNA
molecule whereas there will only be
two copies of the nuclear DNA in
the same cell. This great abundance
of mtDNA in a cell has great
significance for forensic studies as
mitochondrial DNA can therefore be
obtained from smaller samples of
tissue than are needed for the
isolation of nuclear DNA (see page 3).
Where does our mtDNA come from??
Sperm cell - has a nucleus (in the head) with 23 chromosomes, a middle
piece and a tail. The sperm has mitochondria (estimated at 100) concentrated
at the base of the tail to supply the sperm with energy to swim to the egg.
Egg cell - has a nucleus with 23 chromosomes and cytoplasm with
mitochondria (estimated at about 100,000)
At fertilisation the sperm enters the egg and the nuclei fuse (resulting in
the 46 chromosomes), the mid-piece and the tail of the sperm are destroyed
(together with the male mitochondria).
The cytoplasm of the zygote is supplied by the egg cell as the sperm cell had
very little cytoplasm. Thus the mitochondria in the fertilised egg are all from
the mother - so we inherit all of our mtDNA from our mother.
Each of us (male and female) has the same mtDNA as our mother (see
pedigree charts on pages 3 and 4).
When was cytoplasmic DNA discovered??
In the early 1960s a number of experiments showed that mitochondria
always arose from the existing mitochondria in the cytoplasm - they were
self replicating. This lead researchers to investigate how this could happen
and by the end of the decade it was clear that mitochondria had their own
DNA (known as mtDNA). About the same time, chloroplasts too, were
found to contain their own DNA (known as cpDNA).
This information sheet contains both prescriptive and non-prescriptive material.
Leaving Certificate
Biology
H. 2.5.13
Non-nuclear inheritance
e.g. mitochondrial and
chloroplast DNA
Higher Level Extension
Students need to know
about the existence of DNA
in non-nuclear components
of a cell e.g. mitochondrial
DNA and chloroplast DNA
Syllabus (page 25) and
Guidelines for Teachers
(page 44 )
Contents
Page
Syllabus requirements
1
Mitochondrial DNA
1
Origin of our mtDNA
1
Discovery of mtDNA
1
Disease and mtDNA
2
mtDNA and forensics
3
Endosymbiont
Hypothesis
4
Could it all be wrong
4
Chloroplast DNA
4
Ideas for the
Classroom
4
Page 1
T
he history of mitochondrial
DNA and disease goes back
to the 1960s. In Sweden, a
patient was described by a
scientist called Luft: he studied
the patient who ate voraciously,
yet stayed thin, sweating
profusely even in winter. The
scientists involved in the
research showed that the
patients muscle mitochondria
could only make a fraction of the
energy that they should
normally
produce;
the
unconverted fuel was diverted
into heat production. The exact
cause of Luft disease, (only one
other case was identified),
remains unknown but the
scientists had broken new
ground by linking mitochondrial
defects to human disease.
Research continued and by the
late 1980s quite a few
mtDNA-linked disease were
described.
Disease and mtDNA
I
magine your body if half of its
energy releasing facilities
were shut down, an energy crisis
would develop - your brain would
be impaired, your vision would
be dim, your muscles would
twitch spastically or would be
too weak to walk or write and
your heart would be weakened.
It is the tissues with high
demands for energy e.g.
muscle, heart, brain that are
particularly vulnerable to
mitochondrial defects. Some of
the more lethal poisons,
including the cyanides, also act
by blocking mitochondrial
biochemical pathways and that
is why they are so deadly.
A
lso because the respiratory
pathway is disrupted at
some point all the biochemical
steps before the point where
the problem is become backed
up - often leading to abnormal
chemistry that produces toxic
by-products e.g. lactic acid
which is often found in the
blood of patients with
mitochondrial disease.
I
nheritance of these diseases,
caused by mutations in
mtDNA, does not follow any
Mendelian rules. The only rules
that can be counted on are that
a father can’t pass on his
mtDNA mutations and a
mother will pass on her
mtDNA mutations to 100%
of her children.
P
atients with these mtDNArelated diseases usually
have a mixture of normal and
mutant mtDNA - a condition
known as heteroplasmy. A
tissue with 20% mutant
mtDNA suffers different effects
than a tissue with 90% mutant
mtDNA., hence the varying
severity of such a disease
within a family.
E
ven though all of a
woman’s children will
inherit her mtDNA mutations,
that does not make it easy to
predict how severe the disease
will be in each child. This is
because the ratio of mutant to
normal mtDNA passed from
The pedigree table to the right
shows the inheritance of a disease
cau sed by a mu tation in
mitochondrial DNA.
The three affected individuals in
the first generation must have had
an affected mother (not shown).
1. Affected males do not transmit
the trait to any of their children
2. Affected females transmit the
trait to all of their children.
It dies out if a woman has
• no children, or
• all male children
Unaffected male
Affected male
This information sheet contains both prescriptive and non-prescriptive material.
mother to child can vary
dramatically. Because the mother
passes her mitochondria (with
normal and mutated mtDNA)
randomly to all her egg cells, each
zygote produced will receive a
different amount of mutated
mtDNA. A mother with, perhaps,
a mild form of a mitochondrial
disease may give birth to one child
with a very severe disease and a
second child with no disease
symptoms at all.
D
iseases that have been
linked to mutated mtDNA
MIDD - maternally inherited
diabetes with deafness.
NARP - a disease with muscle
weakness, wobbliness and retinal
disorder.
MELAS - headaches, visual and
hearing loss, exercise intolerance
and elevated lactic acid in the
blood.
There are many others being
identified every year and to date
almo st 5 0 d i se a se - cau s in g
mutations have been described.
A
ging and mtDNA - the aging
process is now also thought
be linked to deletions
in
mtDNA. Small amounts of this
mutated mtDNA are found in
normal elderly patients and such
deletions increase exponentially in
long-lived tissues e.g. muscle and
brain. Could mutated mtDNA
have a role in Alzheimer’s or
Parkinson’s diseases??
The ‘mitochondrial theory of
aging’ proposed many years ago
might now have the beginnings of
some experimental support.
Unaffected female
Affected female
Page 2
:
Grandfather
Grandmother
Uncle
Mother
Father
Victim
Sister
Brother-in-law
Nephew
Aunt
Sister
Cousin
Second cousin
Niece
Niece
Second cousin
"
!
!
!
!
!
!
!
!
!
"
#
$
.
%
#
!
45
!
"
!
%
&"622
!
45
!
#
"
!
!
&''&
(
!
#
#
!
*
!
*
*
#
# +
!-(
!
)
!
,
!
#
7
.
3
!
&'9)
#
!
".
!
7
!
*
!
"
/ 5
!
8 ! 04
"
5
!
!
"
.
!
+
.
!
!
#
.
/
!,
!
0
!
!
!
!
!
&1"2223
.
122
This information sheet contains both prescriptive and non-prescriptive material.
%
/
"(
/
.
/
/
!
5
!
.
Page 3
!"
#
%
&##
'
)
-.
#
#
$
$
#
#
#
#
(
*
+
/
%
0
&
)
,
%
1
2
%
%
Origin of mitochondria
The endosymbiont hypothesis proposes that early in evolution, an energy-poor cell engulfed a bacterium with
far more energy-efficient material and ultimately co-opted its functions. Over time the bacteria evolved into
mitochondria. Endosymbiosis was probably critical for the development of large multicellular organisms
including us.
Mitochondria were first recognised as an important subcellular organelle by Altmann in 1890. He called them
‘bioblasts’ and suggested that they might be tiny independent organisms within eukaryotic cells. Altmann
was not as wrong as biologists once believed, as researchers now suggest that mitochondria are the
descendents of ancient prokaryotes that took up residence in eukaryotic cells and provided them with the
ability to oxidise food products and release ATP.
Could it all be wrong??
Mitochondria may not only be inherited through the maternal line, according to new research, published
August 2002, that promises to overturn accepted biological wisdom.
Schwartz and Vissing from Copenhagen have discovered that one of their patients inherited the majority of his
mitochondria from his father. Mitochondria in the sperm from the father were presumed to be destroyed
immediately after fertilisation, leaving behind only those from the mother.
The two researchers made the discovery while trying to discover why one of their patients suffered extreme
fatigue during exercise. The 28-year old man had normal heart and lungs and although his muscles appeared
healthy they noticed that his muscles absorbed very little oxygen. When the examined the genetic sequence of
his mtDNA they discovered 2 mutations - one of which was responsible for his extreme fatigue.
To investigate the mutations further they also sequenced the mtDNA of his mother, father and uncle. To their
surprise, the sequence matched those of the patient’s father and uncle.
Muscle biopsies showed that about 90% of his mitochondria came from his father. However, the mitochondria in
his blood, hair roots and fibroblasts came from his mother. The 2 mutations appear to have arisen
spontaneously during or shortly after fertilisation.
A few other papers were published also suggesting that mtDNA could be sometimes inherited from fathers,
however, most of them have since been disputed and it is claimed that they were based on incorrect data.
The researchers think that inheritance of paternal mitochondria is probably very rare, however, if confirmed by
other researchers, the findings could have huge implications for evolutionary biology and biochemistry.
Chloroplast DNA (cpDNA)
Chloroplasts in plant photosynthetic tissue also have their own DNA - it has the same type structure as
mtDNA i.e. a circular molecule and each chloroplast contains quite a few copies of this cpDNA. Chloroplast
DNA tends to have more base pairs than mtDNA - ranging from 120,000 - 200,000 base pairs.
This DNA codes for some of the proteins required to make the pigments in a plant cell. Mutations in the cpDNA
genes can cause leaf colour variation e.g. in Mirabilis jalapa (Four-o’clock plant) where a defective gene fails to
produce chlorophyll resulting in white leaves. The inheritance of this gene is maternal which was the clue that
led researchers to locate the gene in the chloroplast.
Unlike mtDNA, which is thought to be always inherited maternally, cpDNA is sometimes inherited paternally
e.g. in the conifers. However, cpDNA is most often inherited maternally e.g. in the angiosperms.
This information sheet contains both prescriptive and non-prescriptive material.
Page 4