The Cell Division Challenge to Eukaryogenesis — And to Evolution
In a previous Article, I discussed the irreducible complexity of the eukaryotic cell division machinery. What makes the origins of the eukaryotic cell cycle particularly resistant to evolutionary explanations is that a wide gulf exists between the mechanism of cell division by eukaryotes and that employed by prokaryotic cells — both in terms of the protein components involved, as well as the underlying logic. There is essentially nothing in common between the two systems. As I noted in my paper,
The invagination of the bacterial cell inner membrane is mediated by FtsZ and the other proteins that together comprise the divisome. In eukaryotic cells, by contrast, a contractile ring forms from actin filaments and myosin motor proteins, which pinches the cell’s membrane to form two daughter cells. The mechanisms of segregating DNA in prokaryotes are also significantly different from the manner of segregating genetic material in eukaryotes. During eukaryotic mitosis…the cell’s replicated DNA condenses into distinct chromosomes. These chromosomes are then equally divided and segregated into two daughter cells through a process guided by the spindle apparatus, ensuring each cell receives a complete and identical set of genetic information. The underlying apparatus of these processes, therefore, are quite distinct between prokaryotes and eukaryotes.
Table 1 in the paper (pages 9-10) highlights important differences in the mode of cell division between these two systems.
Bacterial Cell Division Is Irreducibly Complex
For a survey of the mechanisms involved in bacterial cell division, I refer readers to two articles I previously published at Evolution News — Here and Here. Various features of the prokaryotic cell division machinery, much like eukaryotic cell division, exhibit irreducible complexity. For example, in gram-negative organisms, a minimum of ten proteins (FtsA, B, I, K, L, N, Q, W, Z and ZipA) are indispensable for successful division, and therefore have been suggested as potential targets of antibiotic drugs.1,2,3 For economy of space, I refer readers to my previous articles on this for a more detailed discussion of the irreducible complexity of the prokaryotic cell division machinery.
LECA Possessed Modern-Like Cell Cycle Complexity
Phylostratigraphic analysis has revealed that most of the components found in the modern eukaryotic cell cycle were already present in the last eukaryotic common ancestor (LECA). For example, one study revealed that a minimum of 24 of 37 known subunits, co-activators and direct / indirect substrates of the APC/C were present in LECA.4 A similar analysis was carried out on the components of the mitotic checkpoint and their associated functional domains and motifs. They concluded that “most checkpoint components are ancient and were likely present in the last eukaryotic common ancestor.”5 Another study likewise confirmed that the dynactin complex (the activator of cytoplasmic dynein, which is crucial for mitosis) is also a very ancient complex and likely all of its subunits were found in LECA.6 A yet further study, examining ninety different eukaryotic lineages, inferred the evolutionary histories of the proteins involved in the kinetochore network using a method known as Dollo parsimony (which assumes no more than one invention of a protein and infers subsequent losses of that protein based on maximum parsimony).7 They determined that 49 out of 70 proteins were found in LECA.
Given that LECA appears to have possessed most of the cell cycle components, it raises the question of where those components arose from — particularly since there exists such a radical disparity between the mechanisms of cell division in eukaryotes and prokaryotes. As stated previously, there is virtually nothing in common — either in terms of the protein components or underlying logic.
The Eukaryotic Cell Cycle Components Lack Prokaryotic Homologues
In my recent Paper , I sought to determine, using BLAST and other bioinformatics techniques, the extent to which one can identify remote homologues of the eukaryotic cell cycle components among prokaryotes8,9 — in particular, among the Asgard archaea, an archaeal superphylum believed to represent the closest living relatives to eukaryotes.10The result was that, for the vast majority of eukaryotic cell cycle components, no homologues could be identified among prokaryotes, including among the Asgard archaea. The figure below (figure 2 from my paper) shows my findings for those components associated with the anaphase promoting complex / cyclosome (APC/C) and its direct/indirect targets, the mitotic checkpoint, and the kinetochore network (all of which have been inferred, through phylostratigraphic analysis, to have been present in LECA).
As shown in the figure, a vast majority of the eukaryotic cell cycle proteins lack homologues. In those cases where homology could be identified, in most instances only part of the protein exhibited homology (e.g. the kinase domain of Aurora kinase is obviously homologous to other kinases).
The Challenge to Evolution
As I note in my paper,
These results support the hypothesis that the components involved in eukaryotic cell division are substantially de novo eukaryotic innovations that arose sometime after the split with the archaeal lineages. There seems to be no prima facie evidence that the highly distinct cell replication machinery of these two systems are related through descent with modification. The fact that the majority of the components have also been inferred from phylostratigraphic analysis to have been present in LECA (estimated to have lived 1.1 to 2.3 billion years ago) suggests that all eukaryotic proteins associated with cell division came to exist sometime after the eukaryotic split with the archaea but before LECA.11
Moreover
In the window of time available for the origin of eukaryotic cell division control, multiple proteins not only need to evolve into their specifically crafted structures for the purpose of mediating the cell cycle, but they would need to replace the bacterial cell division proteins as well as be assembled into a highly coordinated system — all while maintaining the integrity of the cell division and DNA segregation process.12
Such a transition seems to be particularly implausible given the irreducible complexity of both prokaryotic and eukaryotic systems. Not only would each of the prokaryotic cell division components need to be replaced, but most of the proteins with which they are replaced would need to arise de novo. Even those few proteins that do have homologues in prokaryotes would need to be repurposed, since they serve quite different tasks between the two systems. For example, in prokaryotes, FtsZ (a homologue of Tubulin) assembles to form the contractile ring that facilitates the bifurcation of the parent cell into two daughter cells, whereas its eukaryotic homologue Tubulin (the subunit of microtubules) plays an important role in chromosome segregation during mitosis.
A Cause with Foresight
If undirected processes are incapable of producing the complex machinery associated with mitotic division, is there any other cause that can? As I explain in my paper,
The transition from prokaryotes to eukaryotes is inextricably associated with the creation of new information in the form of genes necessary to code for the expression of the numerous associated proteins (most of which are absent in prokaryotes). Furthermore, the functions of those proteins must be tightly regulated and controlled through various checkpoint mechanisms. To make matters worse for the standard processes of evolutionary biology, the transition must occur through many small and steady incremental steps, each yielding some functional advantage while also retaining the integrity of the cell division apparatus. Yet, as we have seen, many of the necessary processes are irreducibly complex, meaning that many mutually co-dependent changes are needed before a fitness advantage could be realized.
We know from experience that intelligent agents are capable of rapidly introducing new information into a system in order to radically change its fundamental components into a new set of integrated parts that perform some function. Thus, in every other realm of experience, we would routinely attribute such engineered systems to intelligent agency — a cause that possesses foresight and which can plan for the future, visualize complex endpoints and consciously bring together everything needed to actualize a complex endpoint.
The radical disparity that exists between the eukaryotic and prokaryotic cell division machinery is extremely surprising given the standard evolutionary view of gradual, incremental evolution. On the other hand, it is far less surprising given a hypothesis of design. This data thus tends to confirm a teleological framework over an evolutionary one.
Notes
den Blaauwen T, Andreu JM, Monasterio O. (2014) Bacterial cell division proteins as antibiotic targets. Bioorg Chem. 55: 27-38.
Lock RL and Harry EJ. (2008) Cell-division inhibitors: new insights for future antibiotics. Nat Rev Drug Discov.7(4): 324-38.
den Blaauwen T, Andreu JM, Monasterio O. (2014) Bacterial cell division proteins as antibiotic targets. Bioorg Chem. 55:27-38.
Eme L., Trilles A., Moreira D. and Brochier-Armanet C. (2011). The phylogenomic analysis of the anaphase promoting complex and its targets points to complex and modern-like control of the cell cycle in the last common ancestor of eukaryotes. BMC Evolutionary Biology 11: 265. doi:10.1186/1471-2148-11-265
Vleugel M, Hoogendoom E, Snel B, Kops GJPL (2012). Evolution and Function of the Mitotic Checkpoint. Developmental Cell 23: 239-250. doi:10.1016/j.devcel.2012.06.013
Hammesfahr B, Kollmar M (2012). Evolution of the eukaryotic dynactin complex, the activator of cytoplasmic dynein. BMC Evolutionary Biology 12: 95. doi:10.1186/1471-2148-12-95
van Hoof JJE, Tromer E, van Wijk LM, Snel B, Kops GJPL (2017) Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Reports 18(8): 1265-1472. doi:10.15252/embr.201744102
McLatchie J (2024) Phylogenetic Challenges to the Evolutionary Origin of the Eukaryotic Cell Cycle. BIO-Complexity 2024 (4):1–19 doi:10.5048/BIO-C.2024.4.
Zaremba-Niedzwiedzka K, Caceres EF, Saw JH, Bäckström D, Juzokaite L., et. al(2017) Asgard archaea illuminate the origin of eukaryotic cellular complexity. Nature 541(7637): 353-358. doi:10.1038/nature21031
Spang A, Saw JH, Jørgensen SL, Zaremba-Niedzwiedzka K, Martijn J, et. al(2015). Complex archaea that bridge the gap between prokaryotes and eukaryotes. Nature 521(7551): 173- 179. doi:10.1038/nature14447
McLatchie J (2024) Phylogenetic Challenges to the Evolutionary Origin of the Eukaryotic Cell Cycle. BIO-Complexity 2024 (4):1–19 doi:10.5048/BIO-C.2024.4.
Ibid.
