Irreducibly Complex, Bacterial Cell Wall Manufacture Is an Evolutionary Enigma
One of the most incredible features of cellular life is the capability of self-replication. Bacterial cells divide by a process known as binary fission — an amazing feat of engineering, requiring a myriad of different proteins. Several features of bacterial cell division exhibit irreducible complexity. This represents a fundamental challenge to evolutionary explanations of its origins, since a precondition of natural selection is differential survival, and self-replication is itself required for differential survival. Thus, one cannot plausibly appeal to natural selection to explain the origins of bacterial cell division without assuming the existence of the very thing one is attempting to explain. Here, I will focus only on the severing and re-synthesis of the bacterial cell wall.
The Breaking and Manufacture of the Cell Wall
The peptidoglycan cell wall is a rigid structure that surrounds and protects the bacterium, conferring upon the cell structural integrity and shape. As a bacterial cell divides, its cell wall must grow as the cell elongates in preparation for division. In rod-shaped bacteria, this takes place at multiple locations along the cell, whereas in coccus-shaped bacteria, the cell wall grows outward from the FtsZ ring in opposite directions.1 Cell wall growth requires the controlled cleavage of the existing peptidoglycan layer. The β-1,4 glycosidic bonds that link N-acetylglucosamine and N-acetylmuramic acid are hydrolyzed by enzymes called autolysins, which have to be very carefully regulated because they can result in programmed cell death.2,3 Specific regulatory mechanisms guide the localization of autolysins to the site of cell division.4,5,6 These regulatory mechanisms ensure that autolysins are targeted only to the appropriate region of the cell. Autolysins bind to the peptidoglycan at the site of cell division, and catalyze the hydrolysis of the peptide cross-links within the cell wall. This cleavage weakens the peptidoglycan at the division site, allowing the cell wall to undergo controlled breakage. The gaps are then filled in with additional cell wall material.
The first stage of re-synthesis of the cell wall is the formation of the peptidoglycan precursors.7 A chain of five amino acids (a pentapeptide) is added to N-acetylmuramic acid.8 N-acetylglucosamine is subsequently attached to the end of the N-acetylmuramic acid. The result is a peptidoglycan precursor. An extremely hydrophobic molecule, called bactoprenol, is embedded in the inner cytoplasmic membrane.9,10 Bactoprenol shuttles the hydrophilic peptidoglycan precursors from the inner side of the membrane, where they are synthesized, to the outer side of the membrane where they are needed for the assembly of the cell wall. This hydrophobic protein is essential because the hydrophilic precursors cannot easily traverse the hydrophobic membrane on their own.
Once bactoprenol reaches the periplasmic space (in gram-negative bacteria) or the cell exterior (in gram-positive bacteria), it transfers the peptidoglycan precursors to the peptidoglycan assembly site. There, glycosyltransferases and penicillin-binding proteins (also called transpeptidases) utilize these precursors to build the glycan chains and cross-link them to provide the cell wall with stability and strength.11,12 The penicillin-binding proteins are responsible for catalyzing the cross-linking of the peptide side chains between diaminopimelic acid and D-alanine on adjacent peptides. In gram-positive bacteria, cross-links typically occur from an L-lysine to a D-alanine of adjacent peptides. At the end of the peptidoglycan precursor, there exist initially two D-alanine residues, but one is removed during the reaction leaving one in the final molecule. In E. coli a specialized penicillin-binding protein called FtsI is the key player in transpeptidation at the septum.13 Localization of FtsI to the septum itself requires an intact N-terminal membrane anchor in addition to the division proteins FtsZ, FtsA, FtsQ, FtsW, and FtsL.14,15
An Evolutionary Enigma
What about this process is a challenge to evolution? Absolutely critical to cell division in virtually all bacteria is the ability to re-synthesize peptidoglycan. How do we know it is so crucial? The mechanism of action of beta-lactam antibiotics (including penicillin, cephalosporins, and monobactams) is to interfere with the peptidoglycan cross-linking.16,17 As their name implies, penicillin-binding proteins are the target of penicillin, which causes them to lose their enzymatic activity. The activity of the autolysins weakens the cell wall to such an extent that the cell lyses (bursts open). Some other, non beta-lactam, antibiotics (e.g., lactivicins) have a similar mechanism of action.18,19 Antibiotics may also target cell wall precursors. For instance, the antibiotic nisin associates with cell wall precursor lipid II and locks it in a stable complex, thereby effectively inhibiting the peptidoglycan synthesis cycle.20,21
Consider the following two observations:
Critical to the elongation process is the severing of the peptidoglycan cell wall by the autolysins.
Critical to cell viability is the re-synthesis of the peptidoglycan cell wall.
These processes have to be highly coordinated. If the mechanism for severing the cell wall arose without simultaneously having a mechanism in hand to rebuild the cell wall, the cell would not survive the division process. Both mechanisms must arise together. One might object that a mechanism for repairing breaks in the cell wall could have arisen first, before being coopted into the cell division machinery. But without being able to sever the cell wall, there could be no division and thus no differential survival, and by extension no natural selection.
This process of severing and rebuilding the cell wall is critical to cell division in almost all bacteria. A notable exception is species belonging to the genus Mycoplasma, which lack a cell wall. But this has little relevance to accounting for the origins of the mechanisms of severing and rebuilding the peptidoglycan in those species that dopossess a cell wall. As soon as the cell wall — which is a rigid outer layer that provides structural support to the cell — arose, there would need to be a mechanism for re-modelling and splitting it to allow the bacterium to divide into two daughter cells. Moreover, Mycoplasma species are obligate parasites, dwelling in osmotically protected habitats. Furthermore, in place of a cell wall they typically have sterols in their cytoplasmic membrane, which imparts to them greater rigidity and strength.
Foresight Is Required, Pointing to Intelligent Design
In summary, cell wall remodeling and splitting, essential to the cell division process in bacteria, is irreducibly complex, requiring both the mechanism for severing the peptidoglycan and the resynthesis process to arise simultaneously. Without being able to rebuild the cell wall, the cell will burst due to the osmotic pressure. But without being able to sever the peptidoglycan, the cell cannot divide. Evolutionary processes cannot select for some future utility that is only realized after passing through a maladaptive intermediate. This phenomenon therefore requires foresight, and is thus much more probable on the hypothesis of design than it is on mindless chance and necessity.
Notes
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