The physiology and habitat of the last universal common ancestor

The physiology and habitat of the last universal common ancestor

The only empirical way to deduce how life may have emerged is by taking the stance of assuming continuity of biology from its inception to the present day. 3 Building upon this conviction, we have assessed extant types of energy and carbon metabolism for their appropriateness to conditions probably pertaining in those settings of the Hadean planet that fulfil the thermodynamic requirements for life to come into being.



Wood–Ljungdahl (WL) pathways leading to acetyl CoA formation are excellent candidates for such primordial metabolism.

The universal nature of the Wood–Ljungdahl pathway: the touchstone of biology
(a) The molecular make-up of the C1-body branch in the Wood–Ljungdahl pathway is not conserved between aceto- and methanogens
As is evident from figure 1, the reactions forming the WL pathway of aceto- and methanogens are deceptively similar and, at first glance, appear to differ mainly by the detailed chemical nature of their C1-body (formyl, methenyl, methylene and methyl) carriers, tetrahydrofolate (H4F) in acetogens and tetrahydromethanopterin (H4MPT) in methanogens. 

However, acetogenesis appears to be restricted to the bacterial domain, whereas methanogenesis is exclusively found in Archaea (figure 2). This has led to the proposal that it may have been the very diversification of an ancestral hybrid WL pathway into versions eventually yielding acetate or methane as end products (figure 1) that drove the divergence of the last universal common ancestor (LUCA) of all prokaryotes into a bacterial and an archaeal domain.

This is a not trivial problem that is hand-waved away by making a just so guess. Why should that divergence have arisen? 



The supposed distribution of free-energy-conserving metabolisms within the prokaryotes. 
Differently coloured regions refer to the presence of different chemical (and electrochemical) types of quinones (or complete absence thereof for the cases of the grey regions). 

The grey regions can also be interpreted as gaps, which can only be inferred making things up. The divergence clearly falsifies the claim of common ancestry. It is much more reasonable to infer that each clade of bacterias and archaea was made individually, each according to its kind. 

Searches of the genomes of acetogens for enzymes clearly homologous to those of the methanogenic C1-branch came up empty-handed with one notable exception, i.e. the initial step of CO2 reduction which is, in both cases, catalysed by a molybdo/tungstopterin enzyme from the complex iron–sulfur molybdoenzyme (CISM) superfamily. However, even these latter enzymes differ substantially with respect to subunit and cofactor composition. Apart from this reaction, all other subsequent reduction steps of C1-bodies seem to be catalysed by unrelated enzymes in aceto- and methanogens.

The result/evidence basically falsifies/refutes the claim of common ancestry within different bacterias, and also between archaea and bacterias.

This finding makes even clearer the above-mentioned fact that the C1-bodies methenyl, methylene and methyl are carried by dissimilar molecules, methanopterins in methanogens and folates in acetogens

Organic soup scenarios stipulate that sufficient quantities of organic molecules may have been produced in Miller–Urey-type reactions to allow heterotrophy as the ancestral system of biomass production. Apart from all the controversy concerning the soundness of the starting conditions for Miller–Urey experiments, it has in the recent past been argued that organic soup scenarios for the origin of life are severely at odds with the second law of thermodynamics. More recent approaches to life's emergence have consequently concentrated on autotrophic carbon fixation and assumed that one or more of the known extant autotrophic pathways can serve as at least a partial model of how it was first achieved. 

However, at least six distinct autotrophic carbon fixation pathways have been elucidated during the past few decades. 

That observation, of course, once again, is at odds with the claim of common ancestry. 

This multiplicity of pathways inevitably raised the question as to which of these possibly functioned in emerging life. As detailed at the beginning of this article, the WL pathway found in the acetogens and the methanogens is presently favored owing to its simplicity, far-going reliance on inorganic cofactors and chemiosmotic potential-generating second nature.

I wonder why the reliance of inorganic cofactors is a plus for the proposed scenarios, in face of the enormous complexity to synthesize them. 

If this is how life began fixing carbon, we are led to wonder why an ancestral WL pathway has not become life's one and only principle for biomass production.

True. And if a creator would not be excluded a priori, the question or answer would be: Because the creator invented and designed various pathways to get the feat done, and so, showing his inventive power !!  

The multiplicity of autotrophic CO2-fixation pathways therefore indeed represents a major puzzle in current scenarios stipulating an autotrophic origin of life.

There is no puzzle for proponents of intelligent design, however.

The vast majority of present-day methanotrophs, however, use molecular oxygen to oxidize methane. This very fact probably represents the second major obstacle for counting methanotrophy in as a putative primordial energy metabolism.


Denton: Evolution, A Theory in Crisis, page 249
We now know not only of the existence of a break between the living and non-living world, but also that it represents the most dramatic and fundamental of all the discontinuities of nature. Between a living cell and the most highly ordered non-biological system, such as a crystal or a snowflake, there is a chasm as vast and absolute as it is possible to conceive.

Only 355 clusters preserve domain monophyly a These 355 proteins were probably present in LUCA and thus provide a glimpse of LUCA’s genome.

LUCA had 30–100 proteins for ribosomes and translation. LUCA’s genes encode 19 proteins involved in ribosome biogenesis and eight aminoacyl tRNA synthetases, which are also essential for the genetic code to work 2

LUCA lived from gasses. For carbon assimilation, LUCA used the simplest and most ancient of the six known pathways of CO2 fixation, called the acetyl–CoA (or Wood–Ljungdahl) pathway which is increasingly central for our concepts on early evolution because of its chemical simplicity 1 Carbon monoxide (CO) is synthesized by carbon monoxide dehydrogenase (CODH)  The methyl and carbonyl moieties are condensed to an enzyme-bound acetyl group that is removed from a metal cluster in acetyl–CoA synthase (ACS) as an energy-rich thioester. Thioesters harbor chemically reactive bonds that play a crucial role in energy metabolism and in metabolism in general, both modern and ancient.

Life is about harnessing energy. Thioesters b are chemically reactive—they forge direct links between carbon metabolism and energy metabolism (ATP synthesis) as they give rise to acetyl phosphate, the possible precursor of ATP in evolution as a currency of high-energy bonds

Many RNA-modifying enzymes trace to LUCA, particularly the enzymes that modify tRNA. Several of those enzymes are methyltransferases (many SAM dependent), and they remind us that, before the genetic code arose, the four main RNA bases could hardly have been in great supply in pure form because there were no genes or enzymes, only chemical reactions.  Spontaneous synthesis of bases in a real early Earth environment like a hydrothermal vent, an environment that lacks the control of a modern laboratory [124], is not likely to generate the four main bases in pure form. Many side products will accumulate, including chemically modified bases .

Chemical modifications in the tRNA anticodon are essential for codon–anticodon interactions to work. Modifications of the rRNA are concentrated around the peptidyl transferase site and are also essential for tRNA ribosome interactions. It is possible ( how does the author know ?? ) that the genetic code itself arose in the same chemically reactive environment where LUCA arose and that modified bases in tRNA carry the chemical imprint of that environment. New laboratory syntheses of RNA molecules in the origin of life context now also include investigations of modified bases , as it is becoming increasingly clear that these are crucial components at the very earliest phases of molecular and biological evolution.



a In cladistics, a monophyletic group, or clade, is a group of organisms that consists of all the descendants of a common ancestor (or more precisely ancestral population). Monophyletic groups are typically characterised by shared derived characteristics (synapomorphies), which distinguish organisms in the clade from other organisms.

b  In chemistry thioesters are compounds with the functional group R–S–CO–R'. They are the product of esterification between a carboxylic acid and a thiol. In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA. Thioesters are common intermediates in many biosynthetic reactions, including the formation and degradation of fatty acids and mevalonate, precursor to steroids. 

Thioesters and the origin of life

As posited in a "Thioester World", thioesters are possible precursors to life.^[12] As de Duve explains:

It is revealing that thioesters are obligatory intermediates in several key processes in which ATP is either used or regenerated. Thioesters are involved in the synthesis of all esters, including those found in complex lipids. They also participate in the synthesis of a number of other cellular components, including peptides, fatty acids, sterols, terpenes, porphyrins, and others. In addition, thioesters are formed as key intermediates in several particularly ancient processes that result in the assembly of ATP. In both these instances, the thioester is closer than ATP to the process that uses or yields energy. In other words, thioesters could have actually played the role of ATP in a "thioester world" initially devoid of ATP. Eventually, [these] thioesters could have served to usher in ATP through its ability to support the formation of bonds between phosphate groups.

However, due to the high free energy change of thioester's hydrolysis and correspondingly their low equilibrium constants, it is unlikely that these compounds could have accumulated abiotically to any significant extent especially in hydrothermal vent conditions





1. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007518#pgen.1007518.ref051
2. https://sci-hub.tw/https://www.nature.com/articles/nmicrobiol2016116
3. https://royalsocietypublishing.org/doi/10.1098/rstb.2012.0258

Biological cells are high-performance manufacturing systems. They operate a very lean production system. Cells are extremely good at making products with high robustness, flexibility, and efficiency.

In biological cells, all products and machines are built from a small set of common building blocks that circulate in local recycling loops.  Production equipment is added, removed, or renewed instantly when needed. The cell’s manufacturing unit is highly autonomous and reacts quickly to a wide range of changes in the local environment. in biosynthesis, cells apply the just-in-time principle for the making of products and machines (enzymes) that are needed. The cell is quite clearly a manufacturing system. It uses a small set of inputs to “manufacture” a wide range of compounds that help it to interact appropriately with its environment, and eventually allow it to reproduce itself. The cell manages this production in a complex network of several thousands of biochemical reactions. Escherichia coli runs 1,000–1,500 biochemical reactions in parallel. Just as in manufacturing, cell metabolism can be represented by flow diagrams in which raw materials are transformed into final products in a series of operations.. The complexity of the cell’s production flow matches even the most complex industrial production networks we can observe today. The cells production systems are fast, efficient, and responsive to environmental change. Speed and range of response, as well as efficiency of its production systems, are clearly critical to the biological cell.

Cell technology is much older and more mature than any human technology. The cell carries out a very lean6 operation: By using pull systems and excess capacity, the storage of intermediates is kept to a minimum within the pathways. 

Cells store raw materials for bad times, like glycogen in roots or fat tissue. In addition, many organisms store nutrients for their offspring, e.g., in seeds or eggs. These different types of storage represent a “strategic reserve,” not intermediates. 

In biochemical pathways, production occurs only when triggered by a downstream shortage. Or, inversely, any build-up of downstream product will immediately halt further production. As long as there is still final product available, the first enzyme or “machine” of the pathway is physically blocked by an interaction between the final product and the enzyme, a mechanism called “feedback inhibition”. When the final product of a pathway is depleted by high “demand,” the first enzyme is unblocked. As it opens up for production, it gets hold of a piece of raw material and starts processing it. The cell never forecasts demand; it achieves responsiveness through speed, not through inventories. The limits to responsiveness depend only on the capacity limits of the enzymes in a particular pathway. The corresponding mechanism in manufacturing is referred to as a pull system. It produces only in response to actual demand, not in anticipation of forecast demand, thus preventing overproduction.

In virtually all biochemical pathways, the first enzyme is the bottleneck that limits the entry rate. The enzymes within the pathway can process products much faster than the entry rate and, as a result, the level of intermediate products is kept to a minimum. And there is an important logic for that:

The internal space of a cell is limited: With an increase in size, the volume grows much faster than the available surface for exchanging energy and substances with the environment. The ratio of volume that must be fed and supported over surface area available for exchange with the environment sets a cap on the maximal cell size.

The upfront bottleneck  simplify production control in manufacturing. Escherichia coli, for instance, is known to dedicate about 11% of its genes to regulation and control. The cell operates with little waste, even in regulating its pathways. With its 11% of regulatory genes, the cell  sets a pretty tight benchmark for regulation efficiency. 


It is important for the cell to keep intermediates at a low level in order to save energy and building blocks. Work in process, in the form of intermediates, is costly—first, because space comes at a premium in the cell, and second, because inventory may degrade and represents unproductive use of material. The question is whether the cell pays a price for keeping the level of intermediates at such a low level. It does have excess capacity for all but the first enzyme in its pathways, and one may wonder whether this is efficient. 


The cell also uses quality-management techniques used in manufacturing today. The cell invests in defect prevention at various stages of its replication process, using 100% inspection processes, quality assurance procedures, and foolproofing techniques. An example of the cell inspecting each and every part of a product is DNA proofreading. As the DNA gets replicated, the enzyme DNA polymerase adds new nucleotides to the growing DNA strand, limiting the number of errors by removing incorrectly incorporated nucleotides with a proofreading function.  When a wrong nucleotide is added, DNA polymerase possesses an exonuclease activity that removes the wrong nucleotide, thus ensuring correct replication. 

An example of quality assurance can be found in the use of helper proteins, also called “chaperones.” These make sure that newly produced proteins fold themselves correctly, which is critical to their proper functioning. Finally, as an example of foolproofing, the cell applies the key-lock principle to guarantee a proper fit between substrate and enzyme, i.e., product and machine. The substrate fits into a pocket of the enzyme like a key into a lock, ensuring that only one particular substrate can be processed. The pocket is an indentation of the protein into which the substrate fits like a key in a lock.  

The cell’s pathways are designed in such a way that different end products often share a set of initial common steps. For example, in the biosynthesis of aromatic amino acids, a number of common precursors are synthesized before the pathway splits into different final products. 1 This commonality reduces the number of enzymes needed to synthesize amino acids, thus conserving energy and building blocks. It postpones the decision of which amino acid, and how much of it, to synthesize. Another striking example of commonality is steroids, a class of common molecules in microorganisms, plants, and animals. Steroids help in performing various biological functions, such as regulation (hormones) or solubilization of fat (bile acids). Their basic structure is a sterane skeleton, which is modified by side chains and functional groups that give the particular molecule its specific biological activity. Steroids perfectly match the industrial definition.

In biological cells, the basic form of energy, the ATP molecule, is so prevalent that one could describe it as “currency,” in industrial production.

The fundamental “cell technology,” with its production system, has a mature design— i.e., a stable configuration of system components and their interactions.  This does not mean this design is perfect;  and could not be improved upon, but they are stable because they are part of the system. 

The cell uses a small set of basic materials to produce an extremely wide variety of tools and products. As production technologies become more advanced, manufacturing may see a similar convergence around a common set of versatile materials. Four nucleotides, twenty amino acids, some saccharides, and fatty acids are the basic building blocks that are used for the synthesis of major cell molecules: DNA, proteins, polysaccharides, and lipids, respectively. These ingredients of life are so universal that nucleotides, amino acids, saccharides, and fatty acids can easily be exchanged across species, usually when they devour one another. A second, lower level of commonality is found in the central metabolism. Here, a limited number of about 30 intermediates can be identified, which serve as precursors for the abovementioned nucleotides, amino acids, saccharides, fatty acids, and many other biomolecules (Holms 1996). Figure 3 shows a schematic representation of the cell’s component commonality. Interestingly, the intermediates used for “products” and “machines” (enzymes) are identical. In other words, the cell can easily degrade an enzyme into its component amino acids and use these amino acids to synthesize a new enzyme (a “machine”), replenish the central metabolism, or make another molecule (a “product”), e.g., a biogenic amine. It seems an amazing achievement by the cell to build the complexity and variety of life with such a small number of components. Imagine that all industrial machines were made of only 20 different modules, corresponding to the 20 amino acids from which all proteins are made. This modular approach allows the cell to be remarkably efficient and responsive at the same time. Basically, with both products and machines being built from just a few recyclable components, the cell can efficiently produce an enormous variety of products in the appropriate quantities when they are needed. In industry, parts commonality and material versatility are on the rise, but at a very rudimentary level. For example, supply chains are designed with common processes upfront and the differentiating operations at the end. 

The capacity of the cell’s pathways can be adjusted almost immediately if the demand for its products changes. If the current capacity of a pathway is insufficient to meet demand, additional enzymes are “expressed” to generate more capacity within a certain range. Once the demand goes down, these enzymes are broken down again into their basic amino acids. This avoids waste as the released amino acids are then used for the synthesis of new proteins. At any moment, synthesis and breakdown for each enzyme happen in the cell. The constant renewal eliminates the need for other types of “machine maintenance.” Assembly and disassembly of the cell’s machines are so fast and frictionless that they allow a scheme of constant machine renewal. 

The cell does not wait until a protein machine fails, but replaces it long before it has a chance to break down. It completely recycles the machine that is taken out of production. The components derived from this recycling process can be used not only to create other machines of the same type, but also to create different machines if that is what is needed in the “plant.” This way of handling its machines has some clear advantages for the cell. New capacity can be installed quickly to meet current demand. At the same time, there are never idle machines around taking up space or hogging important building blocks. Maintenance is a positive “side effect” of the continuous machine renewal process, thereby guaranteeing the quality of output. Finally, the ability to quickly build new production lines from scratch has allowed the cell to take advantage of a big library of contingency plans in its DNA that allow it to quickly react to a wide range of circumstances.

The cell is highly responsive to change. Its production system can quickly adapt to a wide range of changing conditions and, thus, operate with a high degree of autonomy. This ability is so prominent that one could say that learning from the cell is learning how to quickly respond to change. A fast response to environmental change, such as a change in temperature, a change in the nutrient supply, or the approach of a predator, enables the cell to ensure its survival. A single-cell organism, such as the bacterium Escherichia coli, has encoded in its genes a large potential to adapt to very different environmental conditions. Not all of these genes are constantly expressed; the cell selectively switches them on, depending on the environment, thus changing the associated pathways.

In this way, the cell has a number of “backup plans” in its genetic material. These backup plans are based on the historical experience of the species. They are biologically stored in the genetic material, enabling the organism to react effectively in circumstances “memorized” by the species’ gene pool . Bacteria are able to do even more: They can rearrange their chromosomes by multiple recombinations in response to persistent unfavorable environmental conditions, in a way different from the genetic backup information. The recombinations allow the cell population to create new beneficial gene combinations, and thus new knowledge, out of preexisting chromosome combinations. Of course, lots of individual cells die (those that had the ex post “wrong” recombinations), while the lucky ones survive, and the population as a whole gains.

Cells are autonomous, able to recognize, purify, transform, modify food and uptake it from the outside, and import what they need through sophisticated membrane protein channels. While human made factories require constant external intervention, supply chains, and ways to transport the products to the outside, cells can do it in various ways, like by transport-vesicles, nanotubes, hormones etc

Cells are from the set-go equipped to adapt, change with high robustness, and able to survive to the most hostile environments.

Recycling is a goal-oriented process, namely to economize resources by converting used materials, which otherwise would be thrown out as waste product, into new materials and objects. The cell’s production system takes advantage of closed cycles both within the cell and within the ecosystem of which it is part. The cell recycles building blocks such as nucleotides and amino acids. A so-called scavenger pathway prevents further degradation of nucleotides after the breakdown of DNA and RNA. Proteins are also constantly renewed. Broken-down amino acids are reused to build new proteins. Salvage pathways are used to recover bases and nucleosides that are formed during degradation of RNA and DNA. This is important in some organs because some tissues cannot undergo de novo synthesis. The salvaged bases and nucleosides can then be converted back into nucleotides.

Closed loops exist not only in the cell, but also across the entirety of the living world. Interestingly, the players in the closed cycles in nature are all selfish organisms that perform degradation or synthesis only for their own benefit. Value is created at each step of the cycle in the form of biologically available energy or scarce resources, as in the carbon cycle or the nitrogen cycle. In the carbon cycle, for example, plants form saccharides from airborne carbon dioxide using photosynthesis. As a waste product, oxygen is released. The saccharides serve as a source of energy and building blocks to the plant, representing its profit from this process. Animals eat plants and thus capture the saccharides produced by photosynthesis. They gain energy and building blocks for their metabolism from the plant material they eat, which is their profit from the process. The animals, in turn, use respiration to release a maximum of energy from their nutrition, using oxygen to degrade saccharides to water and carbon dioxide. The carbon dioxide is a waste product for the animal but an input for the plant, whereas the oxygen is waste from photosynthesis but essential for respiration. Each participant in the carbon cycle has its benefit. Each makes a living in the niche it occupies.











1. Aromatic amino acids, phenylalanine, tyrosine, and tryptophane are all synthesized from phosphoenolpyruvate and D-erythrose- 4-phosphate. The pathway branches late at the intermediate chorismate.