Download Genetics of Organelles III GENE330

GENETICS OF ORGANELLES
III.
GENE 330
THE ORIGIN AND EVOLUTION OF
MITOCHONDRIA AND CHLOROPLASTS
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Life on earth originated more than 3 billion years ago. The first
cellular organisms were prokaryotic; they lacked true nuclei and
cytoplasmic organelles and were heterotrophic.
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Eukaryotic organisms evolved 1 to 1.5 billions years ago. The first
known eukaryotes were filamentous green algae, with nuclei and
elaborate intracellular organization, including subcellular
organelles.
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In the 1970 Lynn Margulis forcefully argued that both mitochondria
and chloroplasts were once free-living organisms that became
incorporated into primitive eukaryotic cells.
Eukaryotic Organelles as Endosymbiots
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Symbiosis is a condition in which two or more organisms live together
in close association for their mutual benefit.
Endosymbiosis is a special case in which one of the symbiotic
partners lives inside the other. Evidence from biochemical, genetic, and
molecular studies suggests that mitochondria and chloroplasts
originated as a bacterial endosymbiots.
Mitochondria and chloroplasts are both about the size of some bacteria,
and both contain circular DNA molecules much like bacterial
chromosomes.
Both mitochondria and chloroplasts contain their own distinctive
ribosomes, and both utilize a distinctive RNA polymerase
DNA sequencing studies have demonstrated that some genes in the
mitochondrial and chloroplast DNA are similar to bacterial genes.
All these facts strongly suggest that mitochondria and chloroplasts
originated when bacteria were incorporated into primitive eukaryotic
cells, probably more than a billion years ago.
Eukaryotic Organelles as Endosymbiots
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Since the formation of these relationships, each of the symbiotic partners
has undergone significant changes, and considerable genetic shuffling
has taken place among the mitochondrial, chloroplast, and nuclear
DNAs. For example, in most plant species the small subunit of ribulose
1,5-biphosphate carboxylase is encoded by a nuclear gene, but in some
species of algae, it is encoded by a chloroplast gene.
It has been estimated that between 400 and 2200 of the projected 25 000
genes in the nuclear genome of the plant Arabidopsis thaliana are
derived from bacteria, presumably through transfers from the
endosymbionts that eventually became the mitochondria and chloroplasts
in this species.
Because of this gene shuffling, neither mitochondria nor chloroplasts are
able to sustain themselves without materials specified by the nucleus.
Even major components of the genetic systems of the mitochondria and
chloroplasts are derived from nuclear gene products. These include the
DNA and RNA polymerases, some tRNAs, and many, if not all, of the
ribosomal proteins.
The Evolution of Mitochondria and Chloroplasts
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1.
2.
3.
Variation among the DNAs of mitochondria and chloroplasts
indicates that genomes of these organelles have undergone
significant changes.
First there is variation in gene content. In plants the repertoire of
mitochondrial genes has been augmented by the acquisition of a
large number of unassigned reading frames, noncoding sequences,
and introns. Plant mtDNA molecules are more like the ancestral
condition.
Second, there is structural variation, or variation in the order of
genes within the DNA. For example, human and Drosophila mtDNAs
contain the same set of genes, but these genes are arranged
differently in their respective mtDNAs.
Third, there is variation in the nucleotide sequences of particulars
genes. For example, when we compare the genes for cytochrome b
in human and Drosophila mtDNAs, we find many nucleotide
differences. This kind of variation indicates that the sequences of
these genes have evolved since they diverged from a common
ancestor.
The Evolution of Mitochondria and Chloroplasts
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Geneticists have put considerable effort into studying the rate of
mitochondrial gene evolution and comparing it with the rate of nuclear
gene evolution. The surprising finding is that in some groups of
organisms such as vertebrate animals mitochondrial genes evolve
faster, perhaps 5 to 10 times faster, than nuclear genes. The reason
for this rapid evolution are not clear. Perhaps mitochondrial gene
products are more flexible and are therefore able to tolerate more
amino acid changes than are nuclear gene products, or perhaps the
mutation rate is simply greater in the mitochondria than it is in the
nucleus (due, possibly, to less efficient DNA repair systems in the
mitochondria).
Mitochondria and chloroplasts are almost always transmitted through
the female. There is some evidence for paternal transmission – but it
seems to be infrequent. Thus, the genomes of these organelles evolve
mainly by an asexual process.
Mitochondrial Codes
Differences between the universal genetic code and mitochondrial codes
_____________________________________________________________
Codon
Universal code
Mammals
Mitochondrial codes
Invertebrates Yeasts
Plants
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UGA
Stop
AUA
Ile
CUA
Leu
AGA/AGG Arg
Trp
Met
Leu
Stop
Trp
Met
Leu
Ser
Trp
Met
Thr
Arg
Stop
Ile
Leu
Arg
KEY POINTS
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Mitochondria and chloroplasts seem to have originated as bacteria
that were incorporated into eukaryotic cells about a billion years ago.
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As the endosymbiotic bacteria evolved into organelles, many of their
genes were lost; other genes were transferred into the host cell’s
genome or into the genome of another endosymbiotic bacterium.
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Organellar DNA, especially mtDNA, has been very useful in
studying the evolution of different groups of organisms.
Mitochondrial Diseases
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A large, complex, and heterogeneous group of diseases is caused
by mutations or deletions in human mtDNA.
The clinical spectrum and age of onset of mitochondrial diseases
vary widely.
Organs with high-energy requirements are particularly vulnerable:
brain, heart, skeletal muscle, eye, ear, liver, pancreas, and kidney.
The mutation rate of mtDNA is ten times higher than that of nuclear
DNA.
Mutations accumulate because effective DNA repair and protective
histones are lacking.
At birth most mtDNA molecules are identical (homoplasmy); later
they differ as a result of mutations accumulated in different
mitochondria (heteroplasmy).
Mitochondrial Diseases
Mutations and deletions in mtDNA in man
Both deletions and point mutations are causes of mitochondrial genetic
disorders. Some are characteristic and recur in different, unrelated
patients.
B.
Maternal inheritance of a mitochondrial disease
Hereditary mitochondrial diseases are transmitted only through the
maternal line, since spermatozoa contain hardly any mitochondria. Thus,
the disease will not be transmitted from an affected man to his children.
C.
Heteroplasmy for mitochondrial mutations
Many mutations and deletions in mitochondria are acquired during
an individual’s lifetime. Their proportion may be different in different
tissues (heteroplasmy) and influenced by age. This contributes to the
variability of mitochondrial diseases.
A.
Mitochondrial Diseases
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More than 95% of polypeptides of the respiratory chain are encoded
by genes that reside in nucleus, so one would expect that numerous
mitochondrial disorders would be traced to nuclear mutations.
The most serious disorders usually stem from mutations (or
deletions) that affect genes encoding mitochondrial tRNAs, which
are required for the synthesis of all 13 polypeptides produced in
human mitochondria.
The inheritance of mitochondrial disorders contrasts in several ways
with the Mendelian inheritance of nuclear genes. The mitochondria
present in the cells of a human embryo are derived from
mitochondria that were present in the egg at the time of conception
–mitochondrial disorders are inherited maternally.
Mitochondrial Diseases
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Mitochondrial mutations are particularly likely to accumulate in cells
that remain in the body for long periods of time, such as those of
nerve and muscle tissue. Parkinson’s disease (PD) might be a
consequence of degenerative changes in mitochondrial function.
This possibility originally came to light in the early 1980s when a
number of young drug addicts reported to hospitals with the sudden
onset of severe muscular tremors that are characteristic of advanced
PD. It was discovered, that these individuals had intravenously
injected themselves with a synthetic heroin that was contaminated
with a compound called MPTP. MPTP caused a damage to complex
I of the mitochondrial respiratory chain, leading to the death of nerve
cells in the same region of the brain that is affected in patients with
PD. More recently - pesticides (particularly rotenone) act as
inhibitors complex I (an environmental risk factor for development of
PD?).
mtDNA and Human Diseases
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Recent research has demonstrated that several human diseases are caused
by mitochondrial defects, and in some cases, these defects are due to
mutations in the mtDNA.
One such disease is Leber’s hereditary optic neuropathy (LHON), a
condition characterized by the sudden onset of blindness in adults. This
disease is associated with the death of the optic nerve (at a physiological
level), and with mutation in any of several mitochondrial genes (at a
molecular level). Each mutation changes an amino acid in one of the
mitochondrial proteins – reducing the efficiency of oxidative phosphorylation.
The reduction is great enough to destroy the function of the optic nerve and
cause total blindness. It is not known why this effect is limited to the optic
nerve. LHON is inherited strictly through the maternal line.
Another disorder caused by a mutation in the mtDNA is a Pearson marrowpancreas syndrome, characterized by a loss of bone-marrow cells during
childhood, is frequently fatal. It is caused by a fairly large deletions in the
mtDNA. People with this syndrome almost never have affected parents.
Thus, the causative deletion probably occurs spontaneously during
development in the child or during oogenesis in the mother. Individuals with
Pearson syndrome actually have a mixture of deleted and normal mtDNA –
an example of mitochondrial heteroplasmy. Homoplasmic individuals have
never been observed.
mtDNA to Study Human Evolution
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Some of the most insightful studies of human evolution have
involved the analysis of mtDNA.
There are two reasons why mtDNA is useful: (1) much of it evolves
faster than nuclear DNA, and (2) it is transmitted through the female.
There is relatively little variation in the mtDNA from different human
populations and the greatest variation is found in the mtDNA from
population in Africa.
Given the rate at which mtDNA is know to evolve, these discoveries
suggested that modern human beings originated rather recently,
probably within the last 200,000 years, and probably in Africa.
The mtDNA in all modern groups of humans is descended from an
mtDNA molecule that existed in a single woman who lived in Africa
about 200,000 years ago – “Mitochondrial Eve”.
mtDNA to Study Human Evolution
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However, researchers did not claim that one woman alone gave rise
to all modern human beings. The mass of human nuclear DNA,
which is inherited equally from males and females, and which varies
among the members of a breeding population, cannot be traced to e
single individual.
Migrants from this original African population presumably founded
the early human populations of Europe and Asia, and of others
continents.
This evolutionary scenario has been called the “Out of Africa”
hypothesis.
Another hypothesis proposes that humans evolved simultaneously
in many regions of the world from groups that were long established
in those regions.
mtDNA to Study Human Evolution
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The Neanderthals have always been an enigmatic group
for study of human evolution. Fossils remains indicate
that they were quite different from modern humans:
thicker bones, greater musculature, and different body
proportions clearly set them apart. The questions are:
- were the Neanderthals ancestral to modern human,
- did they interbreed with the populations that
ultimately produced modern humans, or
- were they a separate and distinct species altogether?
In 1997 was published the sequence of 379 bp of mtDNA
extracted from a fossilized Neanderthal arm bone
(fossil's age between 30,000 and 100,000 years) and
amplified by PCR.
mtDNA to Study Human Evolution
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Biochemical analysis of this amplified material showed that
Neanderthal mtDNA differs from modern human mtDNA in 28 of the
379 nucleotides that were analyzed.
The mtDNA isolated from the different modern human typically
shows only 8 nucleotide substitutions in this region.
Thus, Neanderthal mtDNA is significantly unlike that of modern
humans.
Computer analysis of the DNA sequences suggested that the human
and Neanderthal mtDNA lineages began to evolve separately
between 550,000 and 690,000 years ago, and the modern human
mtDNAs originated between 120,000 and 150,000 years ago.
Thus, Neanderthals were almost certainly not ancestral to modern
humans, they evolved separately, and became extinct.
Human Genetics Sidelight – Nucleotide differences within a 379-bp noncoding
region of the mtDNA of a Neanderthal fossil and that of a modern human being.
The following pedigree shows the occurrence and
severity of cardiomyopathy in a family.
© 2003 John Wiley and Sons Publishers