Human genome and

Mitochondrial DNA
The General Organization of the Human Genome

The human genome is the term used to describe the total

genetic information (DNA content) in human cells. It really
comprises two genomes: a complex nuclear genome which
accounts for 99.9995% of the total genetic information, and a
simple mitochondrial genome which accounts for the
remaining 0.0005%.
The nuclear genome provides the great bulk of essential
genetic information, most of which specifies polypeptide
synthesis on cytoplasmic ribosomes.
• Mitochondria possess their own ribosomes and the few
polypeptide-encoding genes in the mitochondrial
genome produce mRNAs which are translated on the
mitochondrial ribosomes.
• However, the mitochondrial genome specifies only a very
small portion of the specific mitochondrial functions;
the bulk of the mitochondrial polypeptides are encoded
by nuclear genes and are synthesized on cytoplasmic
ribosomes, before being imported into the
mitochondria.
 Human Genome

Nuclear DNA Mitochondrial DNA

3300Mb, 30,000 genes 16.6kb, 37 genes

Genes and 2 rRNA 22 tRNA

genes-related Extra-genetic
genes genes 13 polypeptide
sequences DNA
encoding genes
-25% -75%

Unique or low copy

Coding DNA
Non-coding DNA number Moderate to highly repetitive
-10% -90%

Tandemly repeated or Interspersed

clustered repeat repeat

Pseudogenes Gene Introns, untranslated

fragments sequences, etc
Human genes categorized by function of the transcribed proteins, given both as
number of encoding genes and percentage of all genes
 General structure of mtDNA

The human mitochondrial genome is defined by a single

type of circular double-stranded DNA whose complete
nucleotide sequence has been established. It is 16 569 bp in
length and is 44% (G + C). The two DNA strands have
significantly different base compositions: the heavy (H)
strand is rich in guanines, the light (L) strand is rich in
cytosines.
Although the mitochondrial DNA is principally double-
stranded, a small section is defined by a triple DNA strand
structure. This is because a short segment of the heavy
strand is replicated for a second time, giving a structure
known as 7S DNA. Human cells usually contain thousands of
copies of the double-stranded mitochondrial DNA molecule.
Accordingly, although a single mitochondrial DNA duplex has
only about 1/8000 as much DNA as an average sized
chromosome, the total mitochondrial DNA complement can
account for up to about 0.5% of the DNA in a nucleated
somatic cell.
 Mitochondrial DNA
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in
mitochondria. Each mitochondrion is estimated to contain 2–10 mtDNA
copies.
mtDNA is inherited from the mother (maternally inherited, non-
Mendelian). Mechanisms for this include:
• Simple dilution (an egg contains on average 200,000 mtDNA
molecules, whereas a healthy human sperm was reported to contain on
average 5 molecules
• Degradation of sperm mtDNA in the female genital tract, in the
fertilized egg,
• Failure of sperm mtDNA to enter the egg(most mitochondria are
present at the base of the sperm's tail, which is used for propelling the
sperm cells; usually the tail is lost during fertilization)
The human mitochondrial genome
 Inheritance of the mitochondrial genome
• During zygote formation, a sperm cell contributes its nuclear
genome, but not its mitochondrial genome, to the egg cell.
Consequently, the mitochondrial genome of the zygote is
determined exclusively by that originally found in the
unfertilized egg.
• The mitochondrial genome is therefore maternally
inherited(non-Mendelian): males and females both inherit their
mitochondria from their mother but males cannot transmit
their mitochondria to subsequent generations.
• During mitotic cell division, the mitochondrial DNA molecules
of the dividing cell segregate in a purely random way to the two
 Mitochondrial genes
The human mitochondrial genome contains 37 genes: 28 are
encoded by the heavy strand, and nine by the light strand. Of
the 37 genes, a total of 24 specify a mature RNA product: 22
mitochondrial tRNA molecules and two mitochondrial rRNA
molecules, a 23S rRNA (a component of the large subunit of
mitochondrial ribosomes) and a 16S rRNA (a component of the
small subunit of the mitochondrial ribosomes). The remaining
13 genes encode polypeptides which are synthesized on
mitochondrial ribosomes.
Each of the 13 polypeptides encoded by the mitochondrial
genome is a subunit of one of the mitochondrial respiratory
complexes, the multichain enzymes of oxidative phosphorylation
which are engaged in the production of ATP.
However, that there are a total of about 100 different polypeptide
subunits in the mitochondrial oxidative phosphorylation system,
and so the vast majority are encoded by nuclear genes.
All other mitochondrial proteins, including numerous enzymes,
transport proteins, structural proteins etc., are encoded by the
nuclear genome and are translated on cytoplasmic ribosomes
before being imported into the mitochondria.
 genome

Components of oxidative phosphorylation 13 subunits >80 subunits

system

I NADH dehydrogenase 7 subunits >41 subunits

II Succinate CoQ reductase 0 subunits 4 subunits

III Cytochrome b-c1 complex 1 subunit 10 subunits

IV Cytochrome c oxidase complex 3 subunits 10 subunits

V ATP synthase complex 2 subunits 14 subunits

Components of protein synthesis 24 ~80

apparatus

tRNA components 22 tRNAs None

rRNA components 2 rRNAs None

Ribosomal proteins None ~80

Other mitochondrial proteins None All, e.g. mitochondrial DNA polymerase, RNA

polymerase plus numerous other enzymes,

structural and transport proteins, etc.

The genes for mitochondrial ATPase subunits 6 and 8 are partially
overlapping
 Mitochondrial Eve
In human genetics, the name Mitochondrial Eve refers to the matrilineal
most recent common ancestor (MRCA) of all currently living
anatomically modern humans, who is estimated to have lived
approximately 100,000–200,000 years ago. This is the most recent woman
from whom all living humans today descend, on their mother’s side, and
through the mothers of those mothers, and so on, back until all lines
converge on one person. Because all mitochondrial DNA (mtDNA)
generally is passed from mother to offspring without recombination, all
mtDNA in every living person is directly descended from hers by
definition, differing only by the mutations that over generations have
occurred in the germ cell mtDNA since the conception of the original
"Mitochondrial Eve".
Mitochondrial Eve was someone who contributed a vital cell component –
the DNA of the mitochondria – to all of her children, who then passed it to
everyone in future generations.
She lived in sub-Saharan Africa about approximately 170,000 years ago,
about the time period when Homo sapiens split off from other Homo genus
groups.
Through random drift or selection the female-lineage will trace
back to a single female, such as Mitochondrial Eve. In this example
over five generations (colors represent extinct matrilineal lines and
black the matrilineal line) descended from mtDNA MRCA.
Three-parent baby
An artificial reproductive process known as Three Parent In Vitro
Fertilization (TPIVF) results in offspring containing mtDNA from
a donor female, and nuclear DNA from another female and a
male. In the process, the nucleus of an egg is inserted into the
cytoplasm of an egg from a donor female which has had its
nucleus removed, but still contains the donor female's mtDNA.
The composite egg is then fertilized with the male's sperm. The
procedure is used when a woman with genetically defective
mitochondria wishes to procreate and produce offspring with
healthy mitochondria