Irreducible Complexity: The existence of irreducible interdependent structures in biology is an undeniable fact

HIV has undergone every possible combination of 4 mutations, so it's not surprising that it could find gains that require 2, 3, or 4 amino acids at the same time, if each amino acid change doesn't require too many mutations. But probably you don't even need to have them all at the same time though.

"HIV's acquisition of its ability to counteract human tetherin appears to be a stepwise evolutionary gain where mutations gradually improved the ability, since "chimeras within each region yielded intermediate phenotypes. In other words, each mutation made HIV increasingly better at counteracting tetherin. How can it be IC if it's a gradual path?

In other words, each step was advantageous to improve the mechanism.....

The principle of evolutionary continuity, succinctly formulated by Albert Lehninger in his Biochemistry textbook. An adaptation that does not increase the fitness is no longer selected for and eventually gets lost in the evolution (in the current view, only those adaptations that effectively decrease the fitness end up getting lost). Hence, any evolutionary scenario has to invoke – at each and every step – only such intermediate states that are functionally useful (or at least not harmful).

https://onlinelibrary.wiley.com/doi/abs/10.1002/cbdv.200790167

In the end, this is NOT an example of an irreducibly complex system at all as said before. The system lost, and then (re)gained its function.

From pages 55-56 in chapter 3 of Edge of Evolution:
Suppose that P. falciparum needed several separate mutations just to deal with one antimalarial drug. Suppose that changing one amino acid wasn’t enough. Suppose that two different amino acids had to be changed before a beneficial effect for the parasite showed up. In that case, we would have a situation very much like a combination-drug cocktail, but with just one drug. That is, the likelihood of a particular P. falciparum cell having the several necessary changes would be much, much less than the case where it needed to change only one amino acid. That factor seems to be the secret of why chloroquine was an effective drug for decades. How much more difficult is it for malaria to develop resistance to chloroquine than to some other drugs? We can get a good handle on the answer by reversing the logic and counting up the number of malarial cells needed in order to find one that is immune to the drug. For instance, in the case of atovaquone, a clinical study showed that about one in a trillion cells had spontaneous resistance. In another experiment, it was shown that a single amino acid mutation, causing a change at position number 268 in a single protein, was enough to make P. falciparum resistant to the drug. So we can deduce that the odds of getting that single mutation are roughly one in a trillion. On the other hand, resistance to chloroquine has appeared fewer than ten times in the whole world in the past half-century. Nicholas White of Mahidol University in Thailand points out that if you multiply the number of parasites in a person who is very ill with malaria times the number of people who get malaria per year times the number of years since the introduction of chloroquine, then you can estimate that the odds of a parasite developing resistance to chloroquine is roughly one in a hundred billion billion. In shorthand scientific notation, that’s one in 10^20.

page 60: "Recall that the odds against getting two necessary, independent mutations are the multiplied odds for getting each mutation individually. What if a problem arose during the course of life on earth that required a cluster of mutations that was twice as complex as a CCC? (Let’s call it a double CCC.) For example, what if instead of the several amino acid changes needed for chloroquine resistance in malaria, twice that number were needed? In that case the odds would be that for a CCC times itself. Instead of 10^20 cells to solve the evolutionary problem, we would need 10^40 cells."

A "CCC" is Behe's own term. "chloroquine-complexity cluster"
it's what he calls the two simultaneous mutations needed for p. falciparum (the parasite that causes malaria) to evolve resistence to the drug chloroquine.

Can Random Mutations Create New Complex Features?

http://www.evolutionnews.org/2012/06/can_random_muta061221.html

the data suggest many structures might in fact not be evolvable by Darwinian evolution--especially when multiple mutations are needed to convey any advantage on an organism.

In 2004, Michael Behe co-published a study in Protein Science with physicist David Snoke showing that if multiple mutations were required to produce a functional bond between two proteins, then "the mechanism of gene duplication and point mutation alone would be ineffective because few multicellular species reach the required population sizes."

In 2008, Behe and Snoke's critics tried to refute them in the journal Genetics, but failed. The critics found that, in a human population, to obtain only two simultaneous mutations via Darwinian evolution "would take > 100 million years," which they admitted was "very unlikely to occur on a reasonable timescale.

Douglas Axe demonstrated the inability of Darwinian evolution to produce multi-mutation features in a 2010 peer-reviewed study. Axe calculated that when a "multi-mutation feature" requires more than six mutations before giving any benefit, it is unlikely to arise even in the whole history of the Earth.

protein folds in general are multi-mutation features, requiring many amino acids to be fixed before the assembly provides any functional advantage.

Another study by Axe and Ann Gauger found that merely converting one enzyme into a closely related enzyme -- the kind of conversion that evolutionists claim can easily happen -- would require a minimum of seven simultaneous changes,6exceeding the probabilistic resources available for evolution over the Earth's history. This data implies that many biochemical features are so complex that they would require many mutations before providing any advantage to an organism, and would thus be beyond the "edge" of what Darwinian evolution can do.

An empirical study by Gauger and biologist Ralph Seelke similarly found that when merely two mutations along a stepwise pathway were required to restore function to a bacterial gene, even then the Darwinian mechanism failed.7 The reason the gene could not be fixed was because it got stuck on a local fitness maxima, where it was more advantageous to delete a weakly functional gene than to continue to express it in the hope that it would "find" the mutations that fixed the gene.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534379/?fbclid=IwAR0xUgsSkCbFUY6o2TldicIsWbZecPKwjm8r50GFJIeWasedQKL-Tu0hZYI#ppat.1003093.s006

The paper says "the results revealed that four TMD amino acid substitutions (E15A, V19A, I25L and V26L) were sufficient to render the SIVcpz Vpu active against human tetherin". So they are changing amino acids at positions 15, 19, 25, and 26 in that diagram.

Blue is chimp SIV and yellow is human HIV. they mix and match the pieces.

- is no anti-tetherin activity
(+) is a little bit
+ is some
++ is a lot.

In the first column under "release". Note how they never test amino acids 25 and 26 separately. Also note how they never test position 15 separately from either position 19 or position 25-26. Since they didn't test every path, they can't say it is or isn't gradual. Also note that some of the paths they tested were gradual. We go from - to (+) to + to ++. This is on the evolution of HIV-1 group N's anti tetherin activity.

That paper is inconclusive about whether all four amino acids had to change at the same time.

Whole proteins and protein is the level at which there is relevant information about the physical and biochemical aspects of biological function.

Examples of design include molecular-size motors in most living organisms; advanced technologies in cells;b miniature and reliable sonar systems of dolphins, porpoises, and whales; frequency-modulated “radar” and discrimination systems of bats;c efficient aerodynamic capabilities of hummingbirds; control systems, internal ballistics, and the combustion chambers of bombardier beetles'd precise and redundant navigational systems of many birds, fish, and insects;e and especially the self-repair capabilities of almost all forms of life. No component of these complex systems could have evolved without placing the organism at a selective disadvantage until the component’s evolution was complete.

http://www.creationscience.com/onlinebook/ReferencesandNotes39.html?fbclid=IwAR1oys57cpca-VG8E5k8sV-eEYfXGj3jSkFopu6ytKSvcaSdTyClW6q3Lvw

The whole is greater than the sum of its parts is attributed to Aristotle. What he said verbatim, is:

Aristotle, Metaphysics 8.6 [=1045a]
“Concerning the challenge, we just faced about how to describe things in numbers and definitions, What is the reason for a unity/oneness? For however many things have a plurality of parts and are not merely a complete aggregate but instead some kind of a whole beyond its parts, there is some cause of it.

A piston of a motor engine would have no function unless it was created from scratch for a specific function inside the greater system, the engine. In order to achieve that function, it is conceptualized with a specified form and the appropriate materials have to be selected from the start. If for a piston, rather than iron, I select plastic, thermostability will be compromised.  The engine is greater than its parts because of the synergy, the complex system can exercise a higher function. The individual parts have to be conceptualized by someone with foresight, who has the know-how to join the parts to have an emergent function.  

An engineer has to consider those individual parts, and how they have to be formed, in order to ensure and achieve the best performance during operation. He has also to evaluate what materials to use, in order to ensure safety and longevity. He has also to consider how the individual parts will interact with each other. He has to specify the proper sizes and forms. Often, additional considerations come to play. When one subpart of the system has to perform more than one specific function. It can, for example, be part of a feedback system, where its performance rate indicates either if the greater system has to speed up or slow down a manufacturing or operational process.

The same problem-solving processes apply to chemical cell factories. Many, if not most molecular machines, proteins, and enzymes, are substrate-specific. They only interact with very specific substrates. They have advanced sensing mechanisms, or the pocket is tailored to fit only a specific substrate. If molecules of divergent sizes enter the protein, it is expelled. Ribosomes have mechanisms to sort out and filter right-handed amino acids. So it is prevented, that they are incorporated in the elongation process of amino acid synthesis and polymerization.

This all boils down to Behe's argument of irreducible complexity. The advance of science has come to unravel, the emergence of a picture, where systems biology gains more and more relevance. Biology has to be analyzed from a systems perspective.

From a naturalistic perspective, everything is the result of a gradual process that permits the emergence of complexity. From a design perspective, everything is first conceptualized in the mind of God, who has foresight, sets specific goals, knows how to solve all problems in the way, and knows how to instantiate physics, chemistry, and biological systems. Therein lies the big problem for naturalistic, nondesigned proposals. Matter has no foresight. Matter has no goals. Matter does not want to become alive. Matter just remains what it is, without intentions, and based on thermodynamics, it will slowly decompose. That's all.

In a prebiotic soup, or in the ocean, molecules will just randomly float around, and there would never change anything about that behavior. Insisting that they would create specified building blocks, energy, and information storage devices, languages, codes, data, and translation machines, assign meanings to words, and create an alphabet: Such a scenario exists in the realm of fairy tales. Not in real life.

Even if a gene duplication happens, and a batch of nucleotides is copied with a new function, let's say, resulting in a protein or enzyme with a new function: That part has still to be directed to a location inside the cell where it can exercise its new function in a joint venture with other molecules, or substrates. That requires meta-data. Where does THAT come from? Evolution is a simplistic hypothesis for the emergence of complex biological systems, that should have no place anymore in modern science, in the 21st century. Biology should have outgrown from uneducated concepts, based on the limited knowledge from the 19th century, 160 years ago.

Naturalism is a fairy tale for the gullible and uninformed. In the age of information, it is inexcusable to remain ignorant of all these things. Romans 1.19-22 applies more than ever before.

Niall Shanks, Richard Dawkins:  God, the Devil, and Darwin: A Critique of Intelligent Design Theory 2004
http://library.lol/main/4246DEB554A852E1362ACECE795824CF

Cairns-Smith, comparing the pathways of the central biochemistry of organisms with stone arches in which all the components of the arch depend on each other, observed: 

Nowhere is a collaboration of components tighter than in central biochemistry. Pull out a molecule—any molecule ... you will find that every molecule is required in some way or other by every other molecule. ... Nothing can be touched or the whole edifice will collapse. Looking at the structure of interdependencies in central biochemistry it is not at all difficult to see why central biochemistry is now so fixed and has been for so long. The difficult question is how such complexity of arching evolved stone by stone. (1986, 60)

Cairns-Smith remarked: 

‘‘We may make a machine by first designing it, then drawing up a list of components that will be needed, then acquiring the components, and then building the machine. But that can never be the way evolution works. It has no plan. It has no view of the finished system. It would not know in advance which pieces would be relevant. ... It is the whole machine that makes sense of its components’’ (1986, 39). 

The very difference between evolutionary explanations and explanations in terms of intelligent causes is already there in Cairns-Smith’s work. But Cairns-Smith wisely rejected appeals to the supernatural simply to fill in gaps in our knowledge.

It is a sterile stratagem to insert miracles to bridge the unknown. Soluble problems often seem to be baffling, to begin with. Who would have thought a thousand years ago that the size of an atom or the age of the Earth would ever be discovered?... It is silly to say that because we cannot see a natural explanation for a phenomenon that we must look for a supernatural explanation. (It is usually silly anyway.) With so many past scientific puzzles now cleared up, there have to be very clear reasons not to presume natural causes. (1986, 6, my italics)

Cairns-Smith is clearly a methodological and not a metaphysical naturalist. He does not exclude the supernatural but thinks you need more than current ignorance to support the need for explanations involving supernatural intervention. Later in this chapter, we will employ ideas derived from Cairns-Smith’s work to lay this problem of irreducible complexity to rest.

My comment: So Dawkins does not provide an answer to the issue in question. He just resorts to the claim: For every problem in nature, science did find a natural explanation - but provides no example to back up that claim.

Leibniz put it in the Monadology (1714): 
Thus each organic body of a living thing is a kind of divine machine, or natural automaton, which infinitely surpasses all artificial automata. Because a machine which is made by the art of man is not a machine in each of its parts; for example, the tooth of a metal wheel has parts or fragments which as far as we are concerned are not artificial and which have about them nothing of the character of a machine, in relation to the use for which the wheel was intended. But the machines of nature, that is to say living bodies, are still machines in the least of their parts ad infinitum. This it is which makes the difference between nature and art, that is to say, between Divine art and ours. (Parkinson 1977, 189)

My comment: Leibniz gave a remarkable description 300 years ago, that science would come to confirm only about 70 years ago. Each living cell is full of machines, molecular machines, that operate fully autonomously like robots, but the organelles, organs, organ systems, and last not least, the entire body of a multicellular organism operate as machines, on different levels.

Integrated complexity, instantiated to achieve a specific  function is  always caused and implemented by an  intelligent mind

Specified, and irreducible complexity combined, implemented to achieve a specific goal, is prime evidence of intelligent design

Complexity, in special when implemented to achieve a specific purpose, has always only been observed to be the product of a mind. The more complex, the more evidence of design. In ID, complexity is more defined, when we talk about specified, and irreducible complexity. We see it in every living cell, combined. DNA hosts specified complexity, or in words, that can be better comprehended,  instructional assembly information.  EVERY protein, which is the product of the information stored in DNA, is irreducibly complex. In order to perform its basic function, it must have a minimal size. Unless it has it, no deal, no function.  On top of that, proteins are synthesized by the ribosome, depending on the specified complexity of the information stored in DNA.  So on top of irreducible complexity, there is an interdependence of specified, and irreducible complexity combined.

Specified complexity of information stored in DNA, dictates and directs the making of irreducible complex proteins, which all are made to perform a specific function in the cell. On top of that irreducible complexity, there are higher and higher layers of specified, and irreducible complexity. Signaling is essential in every cell, even in single cells, and protists, and was necessary for the first life form to emerge, no matter, what it was. Signals are carriers of information, that are also specified and complex. There has to be always a variegated number of signaling networks in operation, or no life. And there has to be a minimal number of proteins, for life to exist, or no deal. So, proteins are individually irreducible complex, and the cell and its proteome are irreducibly complex because a minimal number of proteins is required for life to exist.

Living cells are prime examples of irreducible and specified complexity, instantiated to perform a specific function. In order for there to be life, a minimal number of parts has to be there, fully implemented, and operational. All at once.

Graham Cairns-Smith:
We are all descended from some ancient organisms or group of organisms within which much of the machinery now found in all forms of life on Earth was already essentially fixed and, as part of that, hooked on today’s so-called ‘molecules of life’. This machinery is enormously sophisticated, depending for its operation on many collaborating parts. The multiple collaboration provides an explanation for why the present system is so frozen now and has been for so long.  So we are left wondering how the whole DNA/RNA/protein control system, on which evolution now so utterly depends, could itself have evolved. We can see that at the time of the common ancestor, this system must already have been fixed in its essentials, probably through a critical interdependence of subsystems. (Roughly speaking in a domain in which everything has come to depend on everything else nothing can be easily changed, and our central biochemistry is very much like that.

Albert-László Barabási:
Various types of interaction webs, or networks, (including protein-protein interaction, metabolic, signaling and transcription-regulatory networks) emerge from the sum of these interactions. None of these networks are independent, instead, they form a ‘network of networks that is responsible for the behavior of the cell. the architectural features of molecular interaction networks within a cell are shared to a large degree by other complex systems, such as the Internet, computer chips, and society.

Wilhelm Huck chemist , professor at Radboud University Nijmegen
A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity

Irreducible complexity, a concept worth to hold.
It speaks of systems, so intricate and fine,
With parts that work together, in a design divine.

The pieces are interdependent, each one with a role,
Removing one of them, the system loses its goal.
A watch with gears and springs, a bird with wings so strong,
The complexity that lies within, can't be proven wrong.

The concept, despite debated, is evidence, of intelligent design,
Its hardly a natural, a product of time,

It's more than just a theory, it's a wonder to behold,
It speaks to us of something, greater than ourselves,
A complexity that's irreducible.

So let us ponder, on this concept so sublime,
And in the irreducible complexity, we find evidence of the divine.

Irreducible complexity, a challenge to Darwin's claims,
A concept that defies, the notion of evolution's aims.
It speaks of systems, so intricate and fine,
With parts that work together, in a design that's divine.

The theory of evolution, relies on gradual change,
But irreducible complexity, presents a range,
Of systems so complex, they cannot be explained,
By gradual steps, they must have formed, complete and unchained.

A watch with gears and springs, a bird with wings so strong,
These examples of complexity, just can't be wrong.
They show us that evolution, can't be the cause,
Of systems so intricate, they leave us in awe.

So irreducible complexity, refutes evolution's might,
It shows us that some things, can't be built up over time.
It speaks to us of something, greater than ourselves,
A complexity that's irreducible, that screams "Intelligent Design".

So let us ponder, on this concept so divine,
And recognize the evidence, of a Creator's design.
For in the beauty of irreducible complexity, we find our grace,
And understand that evolution, cannot take its place.

Why evolution fails

Suppose we have a factory that produces calculators, and we want to examine whether it is possible for the factory to evolve into a computer factory through gradual changes. In this scenario, manufacturing errors occasionally introduce variations in the calculators. If one of these variations happens to improve the calculator's functionality, it gains popularity among users, and the factory incorporates the change permanently. However, the transition from a calculator factory to a computer factory presents substantial challenges. A calculator is a relatively simple device that performs basic arithmetic operations and has a limited number of buttons for numerical input. On the other hand, a computer requires complex processing capabilities, storage, input/output devices, an operating system, and various software applications. Suppose a manufacturing error occurs, resulting in a calculator with slightly more memory or a larger display. While these changes may enhance the calculator's functionality, they would not be sufficient for it to become a computer. Additional components such as a keyboard, storage units, a monitor, and interfaces for peripherals would be required. However, these components cannot be easily modified or duplicated from existing calculator parts. Even if, by chance, a neighboring factory accidentally supplies a computer's motherboard to the calculator factory, numerous specific modifications would still be necessary to integrate it with the existing calculator components. The calculator's buttons would need to be reconfigured as keys, the display would have to be upgraded to a monitor, and various new interfaces and connections would need to be developed from scratch. The transition from a calculator to a computer also involves significant changes in the manufacturing processes and production flow. Computer manufacturing requires advanced techniques such as printed circuit board assembly, soldering, and chip integration, which differ substantially from the processes used in calculator production. The factory would need to acquire new machinery, retrain its workforce, and establish new quality control measures specific to computer production. Moreover, the transition would require the introduction of entirely different raw materials and supply chains. Computer components like integrated circuits, processors, memory modules, and hard drives would need to be sourced and integrated into the production process. This would require establishing relationships with new suppliers, implementing specialized import mechanisms, and incorporating additional testing and validation procedures. Additionally, the factory would need to adapt its production lines and infrastructure to accommodate the assembly of computers. The manufacturing process would become more complex, involving the installation of different components, the integration of software systems, and the testing and quality assurance of the final product. The transition from a calculator factory to a computer factory involves far more than just gradual modifications or adaptations. It requires the integration of specialized components, the development of complex interactions and systems, the acquisition of new machinery, the implementation of advanced manufacturing techniques, the sourcing of different raw materials, and the establishment of new supply chains and quality control measures. While biological evolution through gradual accumulation of unguided errors is a valid concept, applying it directly to the complex transition from a calculator to a computer poses significant challenges that go beyond simple modifications and adaptations within the existing production process.


Let me give you a real-life example:

AIR carboxylase catalyzes the carboxylation of aminoimidazole ribotide (AIR) using bicarbonate (HCO−3/CO2) as the source of the carboxyl group.  Carboxylation refers to the addition of a carboxyl group (-COOH) to a molecule. In the context of biochemical reactions, carboxylation typically involves the addition of a carbon dioxide molecule (CO2) to a substrate, resulting in the formation of a carboxyl group. Carboxylation reactions are common in various metabolic pathways and have important roles in the synthesis of many essential biomolecules. The addition of a carboxyl group can introduce new chemical functionalities, alter the charge or polarity of a molecule, or create binding sites for other molecules or enzymes.

The enzyme AIR carboxylase catalyzes the carboxylation of aminoimidazole ribotide (AIR) using bicarbonate (HCO−3/CO2) as the source of the carboxyl group. This carboxylation reaction leads to the formation of carboxyaminoimidazole ribotide (CAIR), which serves as an intermediate in the synthesis of purine nucleotides.  The carboxylation reaction catalyzed by PurE alone in the purine biosynthesis pathway has a relatively high KM value for bicarbonate (HCO−3), which means that it has a low affinity for the substrate. The KM value represents the concentration of substrate at which the enzyme operates at half of its maximum velocity. KM, or the Michaelis-Menten constant, is a parameter used to describe the affinity of an enzyme for its substrate. It is named after Leonor Michaelis and Maud Menten, who developed the Michaelis-Menten equation to describe enzyme kinetics. The KM value represents the substrate concentration at which an enzyme operates at half of its maximum velocity (Vmax). In other words, it quantifies the concentration of substrate required for an enzyme to achieve half of its catalytic efficiency. Enzymes with a low KM value have a high affinity for their substrate, meaning they can effectively bind and catalyze the reaction even at low substrate concentrations. On the other hand, enzymes with a high KM value have a lower affinity for their substrate and require higher substrate concentrations to achieve the same catalytic efficiency. The KM value is influenced by several factors, including the strength of the enzyme-substrate interaction, the stability of the enzyme-substrate complex, and the rate at which the enzyme converts the substrate into a product. In the context of the carboxylation reaction catalyzed by PurE, the relatively high KM value for bicarbonate indicates that PurE has a lower affinity for bicarbonate. It means that PurE requires a higher concentration of bicarbonate to efficiently catalyze the carboxylation reaction compared to an enzyme with a lower KM value.

In the case of PurE, its high KM value for bicarbonate indicates that it requires a relatively high concentration of bicarbonate to effectively catalyze the carboxylation reaction. The reported KM value of approximately 110 mM suggests that the enzyme would need bicarbonate concentrations around 100 mM to proceed at a reasonable rate. In biochemistry, mM stands for millimolar, which is a unit of concentration. It represents the number of millimoles of a substance per liter of solution. A mole (mol) is a unit used to measure the amount of a substance, and millimole (mmol) is one-thousandth of a mole. Concentrations expressed in millimolar (mM) are commonly used to describe the concentration of solutes in biological systems.  Such a high bicarbonate concentration is considered unphysiological because the intracellular concentration of bicarbonate in cells is typically much lower, ranging from a few millimolar to tens of millimolar. Therefore, if PurE were the sole enzyme responsible for the carboxylation reaction, it would require an excessive amount of bicarbonate that is not typically present in the cellular environment. To overcome this limitation and ensure efficient carboxylation, the purine biosynthesis pathway in organisms like yeast, plants, and most prokaryotes, including E. coli, utilizes a two-protein system consisting of PurE and PurK. PurK acts as a helper protein and interacts with PurE to enhance the efficiency of the carboxylation reaction.

If the helper protein PurK is not present in the purine biosynthesis pathway, and only the enzyme PurE is active, it would have several consequences: PurE alone would still be able to catalyze the carboxylation reaction, but with a lower efficiency. This is because PurK enhances the efficiency of the reaction by reducing the concentration of bicarbonate (HCO−3) required for PurE to function optimally. PurK acts as a helper protein and interacts with PurE to enhance the efficiency of the carboxylation reaction. It reduces the required concentration of bicarbonate by more than 1000-fold, making the reaction more feasible under physiological conditions. Without PurK, PurE would have a higher KM value for bicarbonate, meaning it would require a higher concentration of bicarbonate to achieve the same catalytic efficiency.  This higher bicarbonate requirement would be unphysiological, as it would exceed the typical bicarbonate concentrations found in cells.  Bicarbonate can be produced as a byproduct of various metabolic reactions within the cell. For example, during the breakdown of certain molecules, such as amino acids or carbohydrates, bicarbonate can be generated as part of the metabolic pathway. Consequently, the pathway might be less efficient in converting substrates to products.  The absence of PurK could potentially disrupt the metabolic flux through the purine biosynthesis pathway. The decreased efficiency and higher bicarbonate requirement of PurE alone may lead to a reduction in the production of downstream intermediates and final purine products. This could result in a decreased availability of purines for essential cellular processes such as DNA and RNA synthesis.

There are organisms that have alternative pathways for purine biosynthesis that do not require the helper protein PurK. One example is the archaeon Methanocaldococcus jannaschii, which lacks the PurK protein but still synthesizes purines. The absence of PurK in certain organisms can be attributed to adaptations and the development of alternative enzymatic reactions. These organisms have different mechanisms to achieve the same end result, which is the production of purines. In the case of Methanocaldococcus jannaschii, it has been found that it utilizes a distinct enzyme, known as PurP, to catalyze the carboxylation reaction instead of relying on PurK. PurP is capable of directly carboxylating the purine precursor in a manner that is independent of ATP hydrolysis. The presence or absence of PurK in different organisms likely reflects diversification and adaptation to specific environmental conditions. Organisms lacking PurK may have acquired alternative pathways to optimize their purine biosynthesis based on their unique ecological niches or metabolic requirements.

Methanocaldococcus jannaschii using PurP, and an entirely different enzyme for the same biosynthesis step in purine synthesis

Methanocaldococcus jannaschii, a methanogenic archaeon, uses PurP instead of the traditional PurE and PurK enzymes found in other organisms. The specific reason for this adaptation in Methanocaldococcus jannaschii is related to its unique ecological niche and metabolic requirements. Methanogens are microorganisms that produce methane as a byproduct of their metabolism. They thrive in anaerobic environments, such as deep-sea hydrothermal vents, where they utilize carbon dioxide (CO2) and hydrogen (H2) to produce methane (CH4). This unique metabolic pathway requires efficient utilization of CO2 as a carbon source. PurP, found in Methanocaldococcus jannaschii, has a distinct ability to use CO2 and formate as substrates for the carboxylation step in purine synthesis. This adaptation may be advantageous for Methanocaldococcus jannaschii in environments where CO2 is more abundant or as a means to efficiently incorporate CO2 into essential cellular components, such as purine nucleotides.

Despite catalyzing the same step in purine synthesis, PurP is indeed an entirely different enzyme compared to PurE and PurK. While PurE and PurK are structurally and functionally related enzymes that act as a two-protein system, PurP has and exhibits distinct characteristics. PurP has a different protein structure. It possesses unique catalytic properties, such as utilizing CO2 and formate as substrates instead of bicarbonate. Therefore, while PurP and PurE/K catalyze the same step in purine synthesis, PurP can be considered an enzyme that has emerged independently to fulfill a similar function in different organisms, with structural and functional differences that reflect its unique trajectory of origins. PurP, PurE, and PurK have distinct structural and functional characteristics that allow them to be distinguished from one another.

PurP has a distinct protein structure compared to PurE and PurK. The amino acid sequence and overall folding of PurP are different, resulting in a unique three-dimensional architecture. While PurE and PurK primarily use bicarbonate as a substrate, PurP has a broader substrate specificity. PurP can utilize CO2 and formate as substrates for the carboxylation reaction, distinguishing it from PurE and PurK. The catalytic mechanisms of PurP, PurE, and PurK may differ due to their structural variations and specific active site configurations. These differences may affect how they interact with substrates and carry out the carboxylation reaction. PurP, PurE, and PurK exhibit different levels of catalytic efficiency. Each enzyme has unique kinetic properties, such as turnover rate (kcat) and substrate affinity (KM), which influence their overall efficiency in the purine synthesis pathway.  The genes encoding PurP, PurE, and PurK may have distinct DNA sequences and regulatory elements. Differences in gene expression patterns, transcriptional regulation, and protein synthesis contribute to the differential production and presence of these enzymes in different organisms.  PurP, PurE, and PurK likely have different origins. While PurE and PurK are structurally and functionally related enzymes that form a two-protein system, PurP represents a distinct enzyme that has emerged independently in certain organisms.

The distinct protein structures and catalytic properties of PurP, PurE, and PurK provide compelling evidence that these enzymes were separately designed for their specific functions in different organisms. The remarkable complexity and specificity of these enzymes make it highly unlikely that they could have arisen through a gradual step-by-step evolutionary process. The unique features exhibited by PurP, PurE, and PurK are finely tuned to perform their specific roles in purine synthesis. Any significant changes in their amino acid sequences or protein structures would likely disrupt their functionality, rendering them ineffective or even non-functional. To transition from one species to another, these enzymes would require substantial modifications. However, the probability of random mutations producing the precise sequence and structural changes necessary for functional enzymes in different organisms is astronomically low. The intricate interplay between the amino acid residues and the overall three-dimensional structure of these enzymes is finely balanced and optimized for their respective catalytic activities. Such complex, finely-tuned design and functionality could only be the result of deliberate and purposeful design by an intelligent agent. These enzymes serve their specific functions in different organisms, rather than emerging through an undirected, gradual process of evolution.

Premise 1: Proteins with distinct protein structures, catalytic properties, and functional characteristics require specific amino acid sequences and precise three-dimensional configurations to perform their intended functions effectively.
Premise 2: PurP, PurE, and PurK exhibit distinct protein structures, catalytic properties, and functional characteristics.
Conclusion: Therefore, it is highly improbable for PurP, PurE, and PurK to have a common ancestor because the likelihood of random mutations producing the necessary sequence and structural changes to generate these distinct proteins with their specific functionalities is extremely low.