EVOLUTIONARY ORIGINS OF METABOLIC COMPARTMENTALIZATION IN
EUKARYOTES
The major advantage that metabolic compartmentation has provided is the differential localization and
non-homogenous distribution of biochemical pathways within the cell. Proteins move slower in the
prokaryotic cytosol than in water which is probably the reason behind the fact that subunits of heteromeric
enzyme associate faster if expressed from same location than from distant loci, this might also explain the
origin of formation of operons. Apart from certain exceptions metabolic compartmentation is an attribute
of eukaryotic cells which hints towards endosymbiotic origin of organelles, complex cases arise in algae
due to secondary endosymbiosis which results in complex plastids. Some genes present in plastid and
mitochondrion were transferred to host genome, while mitosomes have lost all their genes to the nucleus;
the proteins were manufactured in the cytosolic ribosome and sent to specific organelles by protein import
apparatus. After the established gene copy of organelle is lost, the functional copy is transferred to the
nucleus until a nuclear copy can compete with the organelle copy. Before the protein import apparatus
arose, the derived gene would be targeted at the cytosol or organelles other than themselves, therefore the
ancestors of plastids and mitochondrion would have contributed to protein complement outside of that
organelle.
Plant nuclear genes that occur as isoenzyme in chloroplast should have come from the ancestral
cyanobacteria via LGT while the cytosolic proteins encoded by the nuclear gene would be related to the
ancestral heritage of the host. As far as we know, there is no evolutionary homing device that
automatically directs the product of the transferred gene back to the original compartment. As a matter of
fact, transferred gene products are free to explore all targeting organelles, they can replace pre-existing
host genes or even pathways if selection favors; or host gene can duplicate to provide organelle with
targeted copies of the host enzyme. Just one enzyme getting targeting ability isn’t of much use because an
intermediate stage with some enzymes of a pathway in the cytosol and some in the organelle is more of a
burden to the cell than benefit. Peroxisomes and glycosomes have entire segments of glycolytic pathway,
this points towards increasing evidence of these being acquired through endosymbiosis else how do we
explain the transfer entire pathways, since achieving 100% pathway specificity is mostly a dream.
But there maybe another way to explain what’s happening. As we know a few percent of the wild type
enzyme is enough to confer wild type phenotype. Using this logic as a cornerstone, we put forth this
hypothesis. Owing to mistargeting of enzymes, tiny quantities of all enzymes will be present in different
compartments, in this way an organelle has all the enzymes to operate a pathway, as natural selection acts
on this organelle, these enzymes start increasing in the given organelle, and the requisite pathway is
established. Multiple targeting of enzymes is in fact a common trait of eukaryotes, and it can be a distinct
possibility to explain transfer of entire pathways and also behave as an intermediate in evolutionary
replacement like the replacement of chloroplast encoded ribosomal protein by nuclear encoded copy of
mitochondrial ribosomal protein. The question as to how dual targeting occurs has multiple possibilities
like alternative transcription, splicing, initiation, post translational modification, etc. since even minor
mistargeting of metabolite transporters is sometimes enough.
In conclusion, I would like to say that protein mistargeting may not only be governed by information
carried by protein but maybe by mRNA too. Retargeting of one protein doesn’t help but mistargeting of a
pinch of an entire pathway might help in the process of metabolic compartmentalization.
