Yes, or might evolve. Having the capacity to carry around and segregate lots and lots of DNA also just gives the eukaryotic cells more options and more flexibility.

The much larger cell size for eukaryotic cells, which seems to be connected with all of the other differences between eukaryotes and bacteria, brings up the issue of the diffusion limit, which Kevin Young wrote about in his contribution to the Forum you recently published on cell size [16]. That was a terrific article, and I agree with everything he said, but I think he didn’t take the argument quite far enough, and that’s what I’m going to do next. His essential point was that bacterial size and structure are constrained by the need to import nutrients efficiently and divide accurately through mechanisms that depend only on diffusion. Even some of the largest bacterial cells we know are still effectively diffusion-limited; for example, Thiomargarita namibiensis appears as a sphere up to 750 μm across, easily visible to the naked eye, but is organized as a very thin shell of cytoplasm, less than 2 μm thick, surrounding a gigantic vacuole [17]. But as soon as you can set up an intracellular molecular transport machinery such as a filamentous cytoskeleton and associated molecular motors, then having the genome be readily accessible to diffusive transport becomes less of an issue, freeing up eukaroytic cells to become physically large.

What we’d really like is some simple, cogent explanation that ties all of these eukaryotic features together: the membrane-enclosed nucleus, the elaboration of other topologically separate membrane-bound compartments, the ability to capture endosymbionts, the ability to make fancy multicellular organisms, the greatly expanded genome, and the large cell size. When I was in graduate school, the explanation was known and it was very straightforward. It was that eukaryotes have a cytoskeleton and bacteria do not. If you go down the list of all the things that are special about eukaryotic cells, you can ascribe virtually all of them to functions of the cytoskeleton. For example, you need structural elements, including microtubules, to organize the membrane-enclosed nucleus and the extensive internal membrane system. And coming back to the expanded genome, we can see that it is simple to divide if you have a mitotic spindle, because adding another chromosome, or even doubling or quadrupling the size of your genome, is no big deal; the mitotic spindle can take care of segregating extra chromosomes using the same mechanism that it uses to segregate just a few. This is because eukaryotic spindles use essentially the same microtubule-kinetochore interface structure repeated for every chromosome, and the collective decisions such as when to enter anaphase are carried out by checkpoint machineries that enforce the rule that all of the kinetochores must be attached before the next step can proceed [18]. In contrast, bacteria that have multiple chromosomes seem to segregate them by using independent, orthogonal machineries specific for each chromosome [19], and don’t appear to have anything as general or as scalable as a mitotic spindle.

Turning to the actin cytoskeleton, this is also vital for many of the eukaryotic-specific features we have discussed. Dynamic actin assembly and disassembly are necessary for phagocytosis, to separate a large membraneous organelle from the plasma membrane compartment, and to also capture an endosymbiont [20]. And then to make a multicellular organism, you need two kinds of interactions between cells. First, you need the ability to lay down an extracellular matrix, which bacteria are also perfectly capable of doing. But then you need some kind of structural elements within cells that can connect to the extracellular matrix and to one another in such a way that forces can be continuously transmitted from the cells to the matrix and from one cell to another. This is the property that is necessary for cells to make simple tissues such as epithelia, where sheets and ensembles of cells can get bigger and bigger and perform coherent behaviors. In animal cells, these processes rely on the actin cytoskeleton [21], and there is evidence that similar cytoskeleton-based processes are also necessary for simpler kinds of multicellularity in non-metazoan eukaryotes such as Dictyostelium[22] and Volvox[23].

The problem with this argument about the basis of the difference between eukaryotes and bacteria is that it all depends on bacteria not having a cytoskeleton, which is what we believed in the early 1990s. But then it was discovered by several very convincing converging lines of evidence, spearheaded by Joe Lutkenhaus, that the bacterial protein FtsZ, which forms a ring around the middle of the bacterial cell and has an essential role in cell division [24], is a homolog of tubulin [25, 26]. And when the atomic structures for both tubulin and FtsZ were solved at the same time, it was absolutely clear that they were nearly superimposable and almost certainly true homologs in the sense of being derived from a common ancestor [27, 28]. So there went the assumption that bacteria do not have a cytoskeleton.

My research up until that point had focused on the actin cytoskeleton, so for a little while I could maintain my eukaryotic-centric world view by saying to myself that bacteria have tubulin but they don’t have actin, and so that must be the most important difference between us and them. But then a few years later, in a series of quite spectacular papers where the cell biological evidence for the shape-determining role of a certain class of bacterial actin-like proteins including MreB [29], was staggeringly confirmed by the undeniable structural similarity between MreB and actin [30], it was quite clearly demonstrated that bacteria do in fact have actin homologs. In the 10 years or so since that discovery, a lot of people have been searching for more different examples of actin and tubulin homologs in bacteria, and indeed we can find a tremendous number of such homologs, a vast proliferation with different biological functions, with various actin homologs like ParM involved in plasmid segregation [31] and MamK necessary for magnetosome alignment [5]. I’m particularly fond of the work of Joe Pogliano, who has gone searching for actins and tubulins carried by plasmids and bacteriophages, and has found an outrageously big zoo of both actins and tubulins [32, 33]. And in a few bacteria, there is even some evidence that they have homologs (or at least functional analogs) of intermediate filament proteins [34]. So we must absolutely acknowledge that the major eukaryotic cytoskeletal proteins are also present in our bacterial comrades, indeed there are many copies of them with distinct biological functions.

So I would like to rephrase the question about what the difference is between eukaryotes and bacteria. We now know that everyone has a cytoskeleton, but still there are fundamental and easily observable morphological differences between these two domains of life, where eukaryotes have used their cytoskeletons to get larger and more morphologically complex and even truly multicellular, while bacteria basically have not done so. So the question I’d really like to ask is, if bacteria have a cytoskeleton, why don’t they do anything more interesting with it?