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284 PLASTIDS, MITOCHONDRIA, AND HYDROGENOSOMES
divergence of the organism harboring the
genes do occur. These non-phylogenetic patterns
can confound tree inference. For these
reasons it has always been desirable to obtain
sequences of other genes to look for congruence
in the phylogenies. Intriguingly, the initial
extra genes, mostly translation-related proteins
such as elongation factors and aminoacyltRNA
synthetases, reaffirmed the rRNA trees.
But other genes have provided a conflicting set
of trees. Tubulin is a universal eukaryotic protein
that forms microtubules, the cytoskeletal
elements in spindles and flagella. Trees of
tubulin sequences place some Archezoa in
non-basal positions. Microsporidian tubulins,
for instance, are strongly allied with those of
fungi, a relatively late-emerging eukaryotic
group. Similarly, Giardia tubulins do not seem
to be basal. How do we rationalize these
conflicting hypotheses? As mentioned above,
patterns other than just phylogenetic patterns
exist in gene sequences. For instance, some
genes in some organisms appear to undergo
accelerated evolution. In trees reflecting
nucleotide (or amino acid) substitution events
as branch lengths, genes with accelerated rates
of evolution can show up as long branches.
Long branches can group together in trees, even
though the organisms from which the longbranch
genes derive are not closely related.
Thus the ‘long-branches-attract’ phenomenon
can posit false relationships or positions
in trees. Could such a ‘long-branches-attract’
phenomenon have confounded the early trees
showing basal Archezoa? Perhaps. The rRNAs,
elongation factors and aminoacyl-tRNA synthetases
of these protists are certainly long
branches, and their basal position might be
an artefact, with their sequences being drawn
down the tree to the similarly long-branch
outgroup sequences (bacterial genes used to
root the eukaryotic sequences). Tubulin genes,
for instance, seem to have (on the whole)
avoided such periods of acceleration and probably
do not show artefactual basal positions.
Parasites of the parabasalid lineage deserve
special mention in a discussion of mitochondrial
origins and evolution. The best known
parasite in this lineage is Trichomonas vaginalis,
a widespread (though relatively benign)
infection of the human genital tract. T. vaginalis
is referred to as a parabasalid because of the
conspicuous Golgi bodies adjacent the basal
bodies of the flagella. Parabasalids lack classic
mitochondria but they do possess a structure,
the hydrogenosome, that appears to have the
same origin as mitochondria. Hydrogenosomes
are round organelles bounded by two membranes
and, as the name suggests, they generate
hydrogen. Like mitochondria, hydrogenosomes
import pyruvate produced by glycolysis. Unlike
mitochondria they do not oxidize this pyruvate
to CO 2 and H 2 O. Rather, they oxidize the
pyruvate to acetate. Electrons from pyruvate
oxidation are transferred not to NADH but
to ferredoxin using a pyruvate ferredoxin
oxidoreductase (PFO) (Chapters 7 and 17).
Ferredoxin is then reoxidized by hydrogenase,
which transfers the electrons onto protons,
producing H 2 . Similar metabolism occurs in
anaerobic bacteria. PFO is the target of a major
drug category. The 5-nitroimidazoles (Metronidazol
and Flagyl) have their nitrate group
activated by PFO. This reactive nitrate then
alkylates surrounding molecules, particularly
DNA, which proves lethal for the parasite.
The 5-nitroimidazoles are thus useful against
Trichomonas. PFO also occurs in some of the
previously discussed anaerobic parasites, such
as Entamoeba and Giardia, and these infections
also respond well to 5-nitroimidazole
therapy. The PFO in Giardia and Entamoeba
is not localized in a hydrogenosome structure
and these organisms do not generate significant
quantities of hydrogen (Chapter 7).
Nevertheless, PFO is a useful drug target.
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA