trans

MITOCHONDRIAL REDUCTION 279
amino acid, and ribosomes with a 70S sedimentation
coefficient, which is the same as bacterial
ribosomes and distinct from the 80S
ribosomes of eukaryotes. Translation by mitochondrial
and plastid ribosomes also exhibits
similar sensitivities to pharmacological agents
as prokaryotic ribosomes. This latter phenomenon
reflects the similar mechanisms and components
participating in this core process, and
will be expanded upon later in the section
exploring drug targets in mitochondria and
plastids. In sum, the majority of what we know
about mitochondria and plastids points to them
being reduced bacteria now living inside
eukaryotic cells.
MITOCHONDRIAL
REDUCTION
The mitochondrial endosymbionts have undergone
substantial modification. Massive reduction,
such as the loss of the wall and large
components of the biosynthetic capacity, probably
stem from redundancy in the new role as
endosymbiont. More interestingly there has
also been massive depletion of the endosymbiont
genome. Typical mitochondrial genomes
only encode a small number of proteins,
whereas a free-living alpha-proteobacterium
probably encodes more than a thousand. Even
accounting for the losses through redundancies,
a typical mitochondrion utilizes an estimated
500 proteins. However, the human
mitochondrion only encodes 13 proteins; yeast
is little better with only eight proteins made
by the mitochondrion. Where are the genes for
the other mitochondrial proteins? In the
nucleus. The host has confiscated most of the
endosymbiont’s genes. The reasons for this
transfer of genetic responsibility are not certain,
but are likely to do with the restricted capacity
for organelle genomes to deal with mutation.
Denied the opportunity for recombination with
other members of their population, mitochondria
have entered a genetic bottleneck. Locked
within its host cell, the mitochondrion has
apparently existed as a clonal line with little or
no opportunity for genetic exchange. Although
one can conceive of some scenario where
mitochondria from two parents might combine
in a newly formed zygote, this does not
appear to occur. Indeed, in most organisms
where mitochondrial descent has been studied
we observe uniparental inheritance of the
organelle. Accumulation of deleterious mutations
may be inevitable, and one solution is
to relocate these essential genes into the host
nucleus, which presumably has occasional
meiosis and the opportunity to remove deleterious
mutations through recombination.
Relocation of the genes, which we refer to
as intracellular gene transfer, can occur by one
of several processes. A common mechanism
seems to be the escape of fragments of the
mitochondrial DNA from the organelle and
their random incorporation into nuclear chromosomes.
Another mechanism involves reverse
transcription of mitochondrial mRNAs to produce
cDNAs that become incorporated into
nuclear chromosomes. These transfers are
apparently ongoing, providing a steady trickle
of genetic transfer between endosymbiont and
host. Eventually some of these transfers result
in active copies of the genes in the nucleus.
Under select circumstances the endosymbiont
gene becomes inactivated and the nuclear
copy takes over.
Transferring genes to the host nucleus may
have avoided some mutational problems, but it
presents an obvious new problem. How can the
gene product be returned to its site of operation?
Messenger RNAs do not seem able to cross
membranes. They exit the nucleus through
nuclear pores, which in effect are very large
openings in the double-membrane envelope
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA