Despite its title, the earlier commentary (‘Why are Bacteria Different from Eukaryotes?’) mostly described how bacteria are different from eukaryotes rather than why. In this commentary, we will cover the ‘why’ part. Please keep in mind that most of these arguments are intelligent guesses and have plenty of room to explore, observe and prove them wrong.
1. Bioenergetics argument - Lane and Martin
We are posting the link to Dan Graur’s blog post, where the argument is presented in a condensed manner. The blog post is a section of his upcoming book on genomics and evolution.
Enigmatically, almost every defining characteristic of eukaryotes is also found in prokaryotes, including nucleus-like structures, recombination, linear chromosomes, internal membranes, multiple replicons, giant cell size, polyploidy, dynamic cytoskeleton, predation, parasitism, introns, intercellular signaling, endocytosis-like processes, and endosymbiosis. It seems as though the prokaryotes made repeated starts up the ladder of complexity, but always fell short. By contrast eukaryotes, despite their meager metabolic repertoire, burst whatever constraints hampered prokaryotes to experiment with the opportunities afforded by greater cell size and more elaborate organization. Why?
The answer, according to Lane and Martin (2010), resides in the bioenergetic changes brought about by the evolution of the mitochondria by endosymbiosis. Broadly speaking, chemical energy in the form of adenosine triphosphate (ATP) is coupled to the transfer of protons (H+ ions) across a membrane. In prokaryotes, ATP synthesis scales with the surface area of the only available membrane, the plasma membrane. In contrast, protein synthesis scales with cell volume. Thus, larger prokaryotic cells are energetically less efficient than smaller ones.
In eukaryotes, energy production is done by hundreds and even thousands of mitochondria, all descended from a singular endosymbiotic event that occurred approximately 1.5 billion years ago. These mitochondria possess highly wrinkled inner membranes, greatly increasing the total surface available for energy-producing oxidative phosphorylation, while at the same time freeing the plasma membrane for other tasks.
Lane and Martin (2010) looked at the amount of power, defined as the amount of energy consumed per unit time, that is available to the cell. In prokaryotes, the available power is of the order of 0.5 pW, where pW stands for picowatt or one trillionth of a Watt. In comparison, the amount of power available to a eukaryotic cell is on average 2,300 pW, i.e., approximately 5,000 times more power that that available to a prokaryotic cell.
How is the energy used in the cell? The energy cost of DNA replication accounts for merely 2% of the energy budget of microbial cells during growth. In contrast, protein synthesis accounts for ~75% of the total energy budget. Thus, in dealing with cell energetics, we need to mainly consider gene expression, and may, as an approximation, ignore everything else. Let us now look at the available power per gene, which was defined as the mean energy available in a cell for expressing one gene per unit time. A prokaryotic gene has on average 0.03 fW of metabolic power, where fW stands for femtowatt, or one quadrillionth of a Watt. In contrast, a eukaryote has on average 57 fW per gene, or about 2000 times more power per gene than a prokaryote. Thus, the most important difference between prokaryotes and eukaryotes is the amount of energy available per gene. We note that the energy allocation per gene is greater in eukaryotes than in prokaryotes despite the fact that eukaryotes have on average 4-6 times more genes than prokaryotes.
What does increased cell complexity entail? The main factor that underlies cell complexity is gene number and to a lesser extent genome size. Can a prokaryotic cell increased its genome size and gene number? If the genome of a prokaryotic cell is increased tenfold in size, the cost of replicating the genome itself would account for about 20% of its energy budget, which under certain conditions may be sustainable. However, if the number of genes is increased tenfold, a huge energy crisis might ensue, whereby the prokaryote would need to drastically reduce the amount of energy it devotes to the synthesis of each of its proteins. The energy allocation per gene may, thus, reach very low levels, maybe too low for viability.
Can the energy supply be increased in prokaryotes? To do that, a prokaryote would need to grow in size, but as mentioned previously the increase in plasma membrane surface will be insufficient to offset the greater demand for protein synthesis due to increase in cell volume.
Mitochondria bestowed upon eukaryotes abundant energy to expand their genomes by orders of magnitude and to greatly increase their genomic repertoire. Genome size in eukaryotes is on average 500 times larger than the mean DNA content in prokaryotic cells, and some 3,000 new protein families are thought to have originated during the prokaryote-to-eukaryote transition. Moreover, the abundant energy produced by the mitochondria allowed eukaryotes to be wasteful. Eukaryotic genomes harbor approximately 12 genes per Mb, compared with about 1,000 in prokaryotes. If an average prokaryote had a eukaryotic gene density, it would encode fewer than 100 genes. Prokaryotes must therefore maintain high gene density, around 500 to 1,000 genes per Mb, and do so by eliminating intergenic and intragenic material, including regulatory elements and microRNAs, by organizing genes into operons, and by restricting the median length of proteins, all of which reduce the energetic costs.
The evolutionary leap from prokaryotes to eukaryotes required orders of magnitude more energy than any prokaryote can offer. For more than three billion years prokaryotes have remained simple because of energy constraints. Throughout prokaryote evolution, natural selection favored small and spare cells with streamlined genomes, rapid reproduction, little superfluous DNA, and tightly disciplined regulation of gene expression. Prokaryotes marched under the banner Small is Beautiful, and in a sense they flourished, multiplied, and inherited the earth. From any point of view except that of a eukaryote chauvinist, the world is a prokaryotic world.
2. Cytoskeleton argument - Julie A Theriot
Julie Theriot instead argues that the motorized cytoskeleton arrays are the primary innovation supporting the novel properties of eukarytoic cells, whereas the energetics is secondary. Quoting from her interview -
So are you going to suggest that bacteria dont have the energy to regulate filament assembly?
Absolutely not. Bacteria have a ton of energy; I dont know of any cases where ATP availability is limiting for any normal biological process.
Could we come back from this prokaryotic chauvinism for a moment to the crucial differences between them and us?
OK, finally I am going to bring this whole argument back full circle and say that really the crucial difference between them and us is the membrane- enclosed nucleus. I think this is probably both a consequence and a cause in a feedback loop mechanism of the diversification of cytoplasmic cytoskeletal structures that then gave rise to larger-scale morphological diversity in eukaryotes. This fourth part of my argument is now much more speculative than even the most speculative parts of what I have said before.
Let us stipulate that it is observable that all cells are organized in some way. What is their central organizing principle? Where is the information that is used by various different components of the cell to know where they are in relationship to everyone else? Well, if you are a bacterium and your chromosome is in the cytoplasm, the chromosome is a spectacular source of spatial information. In most bacteria there are only one or a few chromosomes. They tend to be oriented in a very reproducible way as you go from one individual to the next [103,104] and because of the coupled transcription and translation, the physical site where you have a bit of DNA is also connected to the physical site where you make the RNA and the physical site where you make the protein from that bit of information . If it is important to a bacterial cell to be able to target something to a specific location, it already has all the information it could ever hope for about which location in the cytoplasm is which because it has a well-defined, oriented chromosome present there.
Now, once you wrap that beautifully organized chromosome up in a nucleus, all of a sudden youve lost all that spatial information. It is a very difficult chicken-and-egg problem as to what came first. Was it the wrapping of the nucleus that caused the actin and tubulin cytoskeletons to expand their capacities, or was it the explosion of the capacity of the cytoskeleton that wrapped up the nucleus in membrane? I like to imagine that at some point the nucleus got sequestered away somehow by some sort of prototypical membrane, maybe like what we see now in Gemmata, and then the poor little cytoskeletal elements were left out there in the cytoplasm on their own. They had no way of knowing where they were or of measuring space or position. So they had to figure out how to do it by themselves, without the chromosome there to help. Our eukaryotic cytoskeletons figured out how to do this by setting up large- scale arrays that can be oriented by virtue of having nucleators and molecular motor proteins to make those type B structures that are so useful for spatial organization over vast distances of many tens of micrometers. I think that this is a very elegant solution.
The other benefit that the eukaryotes may have gotten from this strategic decision is extra morphological evolvability. In one of your other interviews, Marc Kirschner made some very interesting points about how certain kinds of preexisting conditions may make it relatively easy for some animal lineages to generate highly variable morphology . I think the eukaryotic cytoskeleton may well be an example of this at the cellular level, an idea that Marc also certainly shares . Once the lonely but inventive eukaryotic cytoskeletal proteins committed to the strategy of using a very small number of filament types to perform a large number of different functions, the addition of a new kind of organizational function to the underlying cytoskeletal framework may have been as simple as coming up with a few new modulators of cytoskeletal filament dynamics, or another kind of slightly modified motor protein. This diversification may have happened very quickly on an evolutionary scale. Sequence analysis of the myosin and kinesin motor families seems to suggest that the most recent common ancestor for all the currently living eukaryotes already had several different kinds of each motor [108,109]. Indeed this most recent common ancestor may even have been capable of both amoeboid crawling motion and flagellar swimming . It may be that the bacteria just never had to face this particular problem because, again, almost universally they have kept their chromosome right there in the cytoplasmic compartment where they could use it for spatial information. So typically, when a particular bacterium needs to make a filamentous structure for a novel purpose, such as orienting the magnetosomes in Magnetospirillum , it duplicates the gene for a cytoskeletal filament and adapts it for that one new purpose. This works fine for the purpose at hand, but forgoes the opportunity for flexibility and truly large-scale cellular organization that are intrinsic features of both the eukaryotic actin and microtubule cytoskeletons.