We Have Been Energy Hogs For a Billion Years

Mitochondria and the origins of eukaryotes.

Last week, we read about the origins of one important characteristic of eukaryotic cells- sex. But there are many more properties that distinguish eukaryotic cells from their bacterial forebears. These include the compartmentalized organelles like mitochondria, chloroplasts, nuclei, golgi, lysozomes, and the endoplasmic reticulum, a vastly expanded and junk-laden nuclear genome with introns, numerous new families of proteins, larger ribosomes, linear DNA with telomeres, separated transcription and translation, and centrosomes / cilia, among others. The mystery is how these many innovative characters all came to happen in one lineage that left no other discernable branches or traces, making the divide between the two forms of life truly gaping and hard to reconstruct. A paper from 2011 provides an illuminating attempt to explain some of these mysteries. Incidentally, it is well-written, and rewards a direct read.

Perhaps one of the most complex, yet at the same time simple, characteristics, is the mitochondrion. Though some eukaryotes live without them, such lineages all are known to have evolved from mitochondrion-containing ancestors. Thus mitochondria are truly part of the original equipment of eukaryotes as far as we currently know. Mitochondria are the descendents of bacteria completely distinct from the proto-eukaryotic host cell, (whether archaeal or something else), and became endosymbionts, whether by some dramatic engulfment / phagocytosis or something more cooperative and intricate. Thus the origin of the mitochondrion is simple- just take in a bacterial partner- even as the organelle and its effects on the host are highly complex. Indeed, mitochondria still have a tiny residual genome, encoding, 37 genes in humans, most of which are tRNAs. While the vast majority of its proteins are encoded far away in the nucleus, it runs its own replication, transcription, and translation apparatus complete with tRNAs and charging enzymes to make 13 proteins of its own, using a genome 1/200,000 the size of the host cell.

Mammalian cell with its nucleus labelled "N" and mitochondria labeled "M".

The current paper proposes that the partnership with mitochondria was the first step on the long road to the eukaryotic cell. The reason is that it is the one enabling change that unleashes all the others, by vastly increasing the energy available to the combined entity. The author goes through a lengthy calculation of the DNA carrying capacity of bacteria, which is clearly limiting and causes a ceaseless competition among bacteria to shorten and streamline their genomes, which account for roughly 2% of cellular metabolism simply for DNA replication, quite apart from all the other costs of gene expression, repair, etc.  Once the host cell convinced the endosymbiont to give up its excess energy (ATP) in return for safety and free food, the race was on to a very profitable division of labor.

If in the combined cell, each mitochondrion supplies the energy equivalent of a bacterium, but with only the genome of an influenza virus, the efficiencies of scale are substantial, perhaps transformative, enabling much larger cells and much larger central genomes. On the other hand, the eukaryotic cell has just as much protein, mRNA and other gene expression apparatus (by mass and energy) as the bacterial cell, (if not more), so the author's focus on the energy available per gene, which results in starting quantitative contrasts between the two domains, is not terribly persuasive.

Example of bacteria (Clostridium) in size comparison to human epithelial cells. The bar is 20 micrometers.

More persuasive is the advantage in membrane area. Bacteria, like mitochondria, manage their short-term energy via a proton motive force over their plasma membranes. Food sources are oxidized, generating electrons which power the pumping of protons out of the cell/organelle. That power, stored much like a battery, is used as needed by ATP-synthesizing machines that run off the power of letting those protons back in. Making a bacterium larger is a losing proposition since the cytoplasmic volume rises by the cube as the surface area rises by the square. While elongation is one solution, and many bacteria are filamentous, spiral, and other long-ish shapes, this poses other obvious problems of safety and internal management. The eukaryotic cell escaped all that by making of the mitochondrion an endlessly replicable internal energy unit, limited only by the host's ability to gather dinner on whatever scale it chooses to operate. And sometimes, operating on a large scale is very profitable.

This hypothesis leads to an interesting theory about the early phases of the symbiosis. However it happened, the earliest mitochondria were fully bacterial, conferring the membrane area advantage, but not the genome streamlining advantage. Given that many mitochondria can exist in each eukaryotic cell (up to several thousand), the advantage of minimizing the infrastructure and energy needed for the maintenance of each one is clear. In the first place, many of the free-living functions would have quickly become unnecessary. Mitochondria today have a complement of about 1000 proteins, far less than the ~ 5,000 proteins found in free-living bacteria. Getting rid of those and the DNA encoding them is a huge savings.

Second, this early mitochondrion would be constantly exposing the host to its own DNA, and the combined entity would gain a streamlining advantage every time the mitochondrion lost a gene that was integrated into the host genome. Putting aside the challenges of transporting all the proteins needed in the mitochondrion back from the host's expression apparatus, which are substantial, every time the mitochondrion lost a gene and had that function supplied externally instead, it became that much more efficient in terms of the genome it was carrying around, in addition to regulatory advantages from being centrally managed by the host.

Comparison of genome sizes, on a log scale. All eukaryotes have larger genomes than all bacteria. Mitochondria, at 16Kb, now fall into the viral range rather than the bacterial range.

Thus a sort of snow-balling process of mitochondrial genome miniturization took place, which had wide-ranging effects. The author speculates that controlling this exposure to external (mitochondrial) DNA, especially its primitive introns, may have led to the nuclear membrane as a form of protection and process management, which in turn created the space for new forms of eukaryotic regulation, like the spliceosomal processing that takes place during exit from the nucleus, and the myriad proteins that are specifically shuttled in and out of the nucleus for regulatory control. Overall, the union of a tiny mitochondrion and a central host genome provides a quantum leap of efficiency, compared to what is possible by scaling up single bacteria in any conceivable way (whether by invaginating their membranes, and / or multiplying their genomes to serve larger surfaces and volumes).

This in turn allowed energetic room for all sorts of new innovations and what a bacterium would regard as waste. A host genome full of introns and other junk DNA, a cytoplasm full of new cytoskeletal proteins devoted to shape control and internal cargo carrying, systems for internal membrane and vesicle management, and diploidy: carrying a full extra copy of its nuclear genome around, as part of the new sexual reproduction cycle. Also:

" The last eukaryotic common ancestor (LECA) had already increased its genetic repertoire by some 3000 novel gene families [over that of the presumed ancestral bacteria]."

Finally, the fact that this series of innovations seems to have happened only once and left no other lineages from along the way makes for a remarkable gap in the evolutionary record, far more profound than that observed around the Cambrian explosion of metazoan life. This paper is very eloquent about the many ways that prokaryotes are trapped in what might be called a version of fiscal austerity, always cutting spending, scrimping on infrastructure, and seeking efficiency über alles. That is no way to live! That any of them found a way out, to the endless vistas of higher complexity and cooperation that now cover the earth with beautiful, rich life, is worthy of wonder and gratitude.

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