Front-loading mitochondria

In the past, I have provided multiple lines of evidence to establish the plausibility of front-loading evolution. However, we have focused primarily on the transition from a unicellular to a multicellular eukaryotic state. Let’s now take one step back and begin pondering whether eukaryotic cells were themselves front-loaded to appear. For without the eukaryotic cell design, it is unlikely that the planet would possess anything analogous to an animal or plant.

While we still don’t really understand the origin of the eukaryotic cell, there is a strong consensus about the origin of the mitochondria, a very important organelle of eukaryotes. According to the endosymbiotic theory, mitochondria are the descendents of bacteria. The theory postulates that a phagocytic cell engulfed some aerobic bacteria and rather than digest them, a symbiotic relationship was established, where each partner benefited from the new relationship. This relationship then set the stage for the ultimate stream-lining of the bacteria, such that they were transformed into mitochondria through the transfer of much of their gadgetry to the host nucleus.

In a nutshell, the essence of the argument for the endosymbiotic origin of mitochondria is that mitochondria look like they share a common ancestor with bacteria. The argument is quite convincing, as there are numerous mitochondrial genes whose sequences are much more similar to bacterial sequence than that which exists in the nucleus of the same cell. In fact, this is an example where no one piece of evidence carries the day, but instead it’s the cumulative power of multiple lines of evidence.

Since mitochondria were once bacteria, might this transition have been front-loaded to happen?

The main obstacle for this transition would occur long after the bacteria had established a symbiotic union with its host. At some point, the bacteria transfer their genes to the host’s nucleus, which would mean the host’s ribosomes in the cytoplasm would have to synthesis the bacterial proteins. And here is where the problem comes in – how do you specifically transfer the bacterial proteins in the cytoplasm, now mixed with the host’s own proteins, back into the proto-mitochondria?

If we think about this transition through the lens of PICERAS, the mitochondria are intimately tied with the pillar of energy, as they regenerate the ATP needed to fuel the cell’s molecular machines. They excel at this function because of the pillar of compartmentalization, where these metabolic reactions are optimized by the localized conditions within the mitochodria brought about by the composition of mitochondrial proteins themselves. So how do we get the mitochondrial proteins that are synthesized by ribosomes in the cytoplasm across the mitochondrial membranes?

Eukaryotic cells use the pillar of seclusion, where mitochondrial proteins have a small set of amino acids attached to the front end of the protein that act as a signal to set them apart from non-mitochondrial proteins. This signal is known as the mitochondrial targeting sequence and contains around thirty amino acids that form an alpha helix that is mostly basic and hydrophobic. Thus, any protein that has this mitochondrial targeting sequence attached to its front end will be transported into the mitochondiria. To go a long way in solving the transport problem posed by the endosymbiotic transition, we need only account for the existence of this mitochondrial targeting sequence, as standard processes of recombination or transposition can paste it onto the front end of any protein.

So where did the mitochondrial targeting sequence come from? Answer – they have always existed in bacteria.  One recent study [1] used two different computer programs to determine that at least one out of every twenty proteins from E. coli possess a mitochondrial targeting sequence. The researchers then took a candidate E. coli protein from the list (YhaR) and expressed it in baker’s yeast. When this was done, the E coli protein was transported to the mitochondria! Not only is this all further evidence of the endosymbiotic theory, the researchers reached the following conclusion:

Multiple sequence alignments of the bacterial versions of these proteins show ragged amino-termini, with YhaR from E. coli having one of the longer amino-terminal extensions. Ectopic expression of bacterial YhaR results in targeting of the protein to yeast mitochondria, suggesting that in some cases, during the course of evolution, this preadaptation meant little or no mutagenesis of upstream regions in bacterial genes to render the proteins they encode competent for import into ‘‘protomitochondria.’’


The gene products translated in the cytosol then needed to be recognized for translocation into protomitochondria. Although seemingly problematic, it is now clear that physicochemical properties of a sizeable number of bacterial proteins like YhaR, present in diverse phyla of extant bacteria and therefore likely to have been inherent in proteins of the ancestral proteobacter, were available as a preadaptation to be used as the basis to specify mitochondrial targeting.

A key phase in the evolution of mitochondria was made possible because of preadaptation. We thus have our first plausible example of front-loading the evolution of the modern, eukaryotic cell.

1. Rebecca Lucattini, Vladimir A. Likic´, and Trevor Lithgow. 2004. Bacterial Proteins Predisposed for Targeting to Mitochondria. Mol. Biol. Evol. 21:652–658.

One response to “Front-loading mitochondria

  1. Tipsy McStagger

    do you know if AdR has commented on this?
    That’s pretty powerful evidence. The mitochondrial targeting sequence existing in prokaryotes…. and then being able to take a bacterial protein, place it in the context of a eukaryote and have that targeting sequence carry it to the eukaryotes mitochondria? that’s pretty cool.

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