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Tuesday, 20 June 2017

Between physics and abiogenesis an unbridgeable chasm?

The Origin of Life, Self-Organization, and Information
Brian Miller

In an  article here yesterday, I described the thermodynamic challenges to any purely materialistic theory for the origin of life. Now, I will address one of the most popular and misunderstood claims that the first cell emerged through a process that demonstrated the property known as self-organization.

As I mentioned in the previous article, origin-of-life researchers often argue that life developed in an environment that was driven far from equilibrium, often referred to as a non-equilibrium dissipative system. In such systems, energy and/or mass constantly enters and leaves, and this flow spontaneously generates “order” such as the roll patterns in boiling water, the funnel of a tornado, or wave patterns in the Belousov-Zhabotinsky reaction. The assertion is that some analogous type of self-organizational process could have created the order in the first cell. Such claims sound reasonable at first, but they completely break down when the differences between self-organizational order and cellular order are examined in detail. Instead, the origin of life required complex cellular machinery and preexisting sources of information.

The main reason for the differences between self-organizational and cellular order is that the driving tendencies in non-equilibrium systems move in the opposite direction to what is needed for both the origin and maintenance of life. First, all realistic experiments on the genesis of life’s building blocks produce most of the needed molecules in very small concentrations, if at all. And, they are mixed together with  contaminants, which would hinder the next stages of cell formation. Nature would have needed to spontaneously concentrate and purify life’s precursors. However, the natural tendency would have been for them to diffuse and to mix with other chemicals, particularly in such environments as the bottom of the ocean.

Concentration of some of life’s precursors could have taken place in an evaporating pool, but the contamination problem would then become much worse since precursors would be greatly outnumbered by contaminants. Moreover, the next stages of forming a cell would require the concentrated chemicals to dissolve back into some larger body of water, since different precursors would have had to form in different locations with starkly different initial conditions. In  his  book on Origins, Robert Shapiro described these details in relation to the exquisite orchestration required to produce life.

In addition, many of life’s building blocks come in both right and left-handed versions, which are mirror opposites. Both forms are produced in all realistic experiments in equal proportions, but life can only use one of them: in today’s life, left-handed amino acids and right-handed sugars. The  origin of life would have required one form to become increasingly dominant, but nature would drive a mixture of the two forms toward equal percentages, the opposite direction. As a related but more general challenge, all spontaneous chemical reactions move downhill toward lower free energy. However, a large portion of the needed reactions in the origin and maintenance of life move uphill toward higher free energy. Even those that move downhill typically proceed too slowly to be useful. Nature would have had to reverse most of its natural tendencies in any scenario for extended periods of time. Scientists have never observed any such event at any time in the history of the universe.

These challenges taken together help clarify the dramatic differences between the two types of order:

Self-organizational processes create order (i.e. funnel cloud) at the macroscopic (visible) level, but they generate entropy at the microscopic level. In contrast, life requires the entropy at the cellular size scale to decrease.
Self-organizational patterns are driven by processes which move toward lower free energy. Many processes which generate cellular order move toward higher free energy.
Self-organizational order is dynamic — material is in motion and the patterns are changing over time. The cellular order is static — molecules are in fixed configurations, such as the sequence of nucleotides in DNA or the structure of cellular machines.
Self-organizational order is driven by natural laws. The order in cells represents specified complexity — molecules take on highly improbable arrangements which are not the product of natural processes but instead are arranged to achieve functional goals.
These differences demonstrate that self-organizational processes could not have produced the order in the first cell. Instead, cellular order required molecular machinery to process energy from outside sources and to store it in easily accessible repositories. And, it needed information to direct the use of that energy toward properly organizing and maintaining the cell.

A simple analogy will demonstrate why machinery and information were essential. Scientists often claim that any ancient energy source could have provided the needed free energy to generate life. However, this claim is like a couple returning home from a long vacation to find that their children left their house in complete disarray, with clothes on the floor, unwashed dishes in the sink, and papers scattered across all of the desks. The couple recently heard an origin-of-life researcher claim that order could be produced for free from any generic source of energy. Based on this idea, they pour gasoline on their furniture and then set it on fire. They assume that the energy released from the fire will organize their house. However, they soon realize that unprocessed energy creates an even greater mess.

Based on this experience, the couple instead purchase a solar powered robot. The solar cells process the energy from the sun and convert it into useful work. But, to the couple’s disappointment the robot then starts throwing objects in all directions. They look more closely at the owner’s manual and realize they need to program the robot with instructions on how to perform the desired tasks to properly clean up the house.

In the same way, the simplest cell required machinery, such as some ancient equivalent to ATP synthase or chloroplasts, to process basic chemicals or sunlight. It also needed proteins with the proper information contained in their amino acid sequences to fold into other essential cellular structures, such as portals in the cell membrane. And, it needed proteins with the proper sequences to fold into enzymes to drive the metabolism. A key role of the enzymes is to  link reactions moving toward lower free energy (e.g. ATP → ADP + P) to reactions, such as combining amino acids into long chains, which go uphill. The energy from the former can then be used to drive the latter, since the net change in free energy is negative. The free-energy barrier is thus overcome.

However, the energy-processing machinery and information-rich proteins were still not enough. Proteins eventually break down, and they cannot self-replicate. Additional machinery was also needed to constantly produce new protein replacements. Also, the proteins’ sequence information had to have been stored in DNA using some  genetic code, where each amino acid was represented by a series of three nucleotides know as a codon in the same way English letters are represented in Morse Code by dots and dashes. However,  no identifiable physical connection exists between individual amino acids and their respective codons. In particular, no amino acid (e.g., valine) is much more strongly attracted to any particular codon (e.g., GTT) than to any other.  Without such a physical connection, no purely materialistic process could plausibly explain how amino acid sequences were encoded into DNA. Therefore, the same information in proteins and in DNA must have been encoded separately.

In addition, the information in  DNA is decoded back into proteins  through the use of ribosomes, tRNAs, and special enzymes called aminoacyl tRNA sythetases (aaRS). The aaRSs bind the correct amino acids to the correct tRNAs associated with the correct codons, so these enzymes contain the decoding key in their 3D structures. All life uses this same process, so the first cell almost certainly functioned similarly. However, no possible connection could exist between the encoding and the decoding processes, since the aaRSs’ structures are a result of their amino acid sequences, which happen to be part of the information encoded in the DNA. Therefore, the decoding had to have developed independently of the encoding, but they had to use the same code. And, they had to originate at the same time, since each is useless without the other.


All of these facts indicate that the code and the sequence information in proteins/DNA preexisted the original cell. And, the only place that they could exist outside of a physical medium is in a mind, which points to design.

Monday, 19 June 2017

Actually,it is rocket science.

Rocket Science in a Microbe Saves the Planet
Evolution News & Views

Anammox. It's a good term to learn. Wikipedia's first paragraph stresses its importance:

Anammox, an abbreviation for ANaerobic AMMonium OXidation, is a globally important microbial process of the nitrogen cycle. The bacteria mediating this process were identified in 1999, and at the time were a great surprise for the scientific community. It takes place in many natural environments... [Emphasis added.]

And now, the news. A team of European scientists found something very interesting about the bacteria. Publishing in Nature, the researchers tell how they have ascertained the structure of a molecular machine that performs chemical wizardry using rocket science.

Anaerobic ammonium oxidation (anammox) has a major role in the Earth's nitrogen cycle and is used in energy-efficient wastewater treatment. This bacterial process combines nitrite and ammonium to form dinitrogen (N2) gas, and has been estimated to synthesize up to 50% of the dinitrogen gas emitted into our atmosphere from the oceans. Strikingly, the anammox process relies on the highly unusual, extremely reactive intermediate hydrazine, a compound also used as a rocket fuel because of its high reducing power. So far, the enzymatic mechanism by which hydrazine is synthesized is unknown. Here we report the 2.7 Å resolution crystal structure, as well as biophysical and spectroscopic studies, of a hydrazine synthase multiprotein complex isolated from the anammox organism Kuenenia stuttgartiensis. The structure shows an elongated dimer of heterotrimers, each of which has two unique c-type haem-containing active sites, as well as an interaction point for a redox partner. Furthermore, a system of tunnels connects these active sites. The crystal structure implies a two-step mechanism for hydrazine synthesis: a three-electron reduction of nitric oxide to hydroxylamine at the active site of the γ-subunit and its subsequent condensation with ammonia, yielding hydrazine in the active centre of the α-subunit. Our results provide the first, to our knowledge, detailed structural insight into the mechanism of biological hydrazine synthesis, which is of major significance for our understanding of the conversion of nitrogenous compounds in nature.

Dinitrogen gas (N2) is a tough nut to crack. The atoms pair up with a triple bond, very difficult for humans to break without a lot of heat and pressure. Fortunately, this makes it very inert for the atmosphere, but life needs to get at it to make amino acids, muscles, organs, and more. Nitrogenase enzymes in some microbes, such as soil bacteria, are able break apart the atoms at ambient temperatures (a secret agricultural chemists would love to learn). They then "fix" nitrogen into compounds such as ammonia (NH3) that can be utilized by plants and the animals that eat them. To have a nitrogen cycle, though, something has to return the N2 gas back to the atmosphere. That's the job of anammox bacteria.

Most nitrogen on earth occurs as gaseous N2 (nitrogen oxidation number 0). To make nitrogen available for biochemical reactions, the inert N2 has to be converted to ammonia (oxidation number −III), which can then be assimilated to produce organic nitrogen compounds, or be oxidized to nitrite (oxidation number +III) or nitrate (+V). The reduction of nitrite in turn results in the regeneration of N2, thus closing the biological nitrogen cycle.

Let's take a look at the enzyme that does this, the "hydrazine synthase multiprotein complex." Rocket fuel; imagine! No wonder the scientific community was surprised. The formula for hydrazine is N2H4. It's commonly used to power thrusters on spacecraft, such as the Cassini Saturn orbiter and the New Horizons probe that went by Pluto recently. Obviously, the anammox bacteria must handle this highly reactive compound with great care. Here's their overview of the reaction sequence. Notice how the bacterium gets some added benefit from its chemistry lab:

Our current understanding of the anammox reaction (equation (1)) is based on genomic, physiological and biochemical studies on the anammox bacterium K. stuttgartiensis. First, nitrite is reduced to nitric oxide (NO, equation (2)), which is then condensed with ammonium-derived ammonia (NH3) to yield hydrazine (N2H4, equation (3)). Hydrazine itself is a highly unusual metabolic intermediate, as it is extremely reactive and therefore toxic, and has a very low redox potential (E0′ = −750 mV). In the final step in the anammox process, it is oxidized to N2, yielding four electrons (equation (4)) that replenish those needed for nitrite reduction and hydrazine synthesis and are used to establish a proton-motive force across the membrane of the anammox organelle, the anammoxosome, driving ATP synthesis.

We've discussed ATP synthase before. It's that rotary engine in all life that runs on proton motive force. Here, we see that some of the protons needed for ATP synthesis come from the hydrazine reaction machine. Cool!

What does the anammox enzyme look like? They say it has tunnels between the active sites. The "hydrazine synthase" module is "biochemically unique." Don't look for a common ancestor, in other words. It's part of a "tightly coupled multicomponent system" they determined when they lysed a cell and watched its reactivity plummet. Sounds like an irreducibly complex system.

The paper's diagrams of hydrazine synthase (HZS) show multiple protein domains joined in a "crescent-shaped dimer of heterotrimers" labeled alpha, beta, and gamma, constituted in pairs. The machine also contains multiple haem units (like those in hemoglobin, but unique) and "one zinc ion, as well as several calcium ions." Good thing those atoms are available in Earth's crust.

Part of the machine looks like a six-bladed propeller. Another part has seven blades. How does it work? Everything is coordinated to carefully transfer electrons around. This means that charge distributions are highly controlled for redox (reduction-oxidation) reactions (i.e., those that receive or donate electrons). The choice of adverbs shows that their eyes were lighting up at their first view of this amazing machine. Note how emotion seasons the jargon:

Intriguingly, our crystal structure revealed a tunnel connecting the haem αI and γI sites (Fig. 3a). This tunnel branches off towards the surface of the protein approximately halfway between the haem sites, making them accessible to substrates from the solvent. Indeed, binding studies show that haem αI is accessible to xenon (Extended Data Fig. 4c). Interestingly, in-between the α- and γ-subunits, the tunnel is approached by a 15-amino-acid-long loop of the β-subunit (β245-260), placing the conserved βGlu253, which binds a magnesium ion, into the tunnel.

We would need to make another animation to show the machine in action, but here's a brief description of how it works. The two active sites, connected by a tunnel, appear to work in sequence. HZS gets electrons from cytochrome c, a well-known enzyme. The electrons enter the machine through one of the haem units, where a specifically-placed gamma unit adds protons. A "cluster of buried polar residues" transfers protons to the active center of the gamma subunit. A molecule named hydroxylamine (H3NO) diffuses into the active site, assisted by the beta subunit. It binds to another haem, which carefully positions it so that it is "bound in a tight, very hydrophobic pocket, so that there is little electrostatic shielding of the partial positive charge on the nitrogen." Ammonia then comes in to do a "nucleophilic attack" on the nitrogen of the molecule, yielding hydrazine. The hydrazine is then in position to escape via the tunnel branch leading to the surface. Once they determined this sequence, a light went on:

Interestingly, the proposed scheme is analogous to the Raschig process used in industrial hydrazine synthesis. There, ammonia is oxidized to chloramine (NH2Cl, nitrogen oxidation number −I, like in hydroxylamine), which then undergoes comproportionation with another molecule of ammonia to yield hydrazine.

(But that, we all know, is done by intelligent design.)


So here's something you can meditate on when you take in another breath. The nitrogen gas that comes into your lungs is a byproduct of an exquisitely designed, precision nanomachine that knows a lot about organic redox chemistry and safe handling of rocket fuel. This little machine, which also knows how to recycle and reuse all its parts in a sustainable "green" way, keeps the nitrogen in balance for the whole planet. Intriguing. Interesting. As Mr. Spock might say, fascinating.

Saturday, 17 June 2017

Why the quest to reduce biology to chemistry is doomed.

The White Space in Evolutionary Thinking


Old CW chance and necessity did it/New CW gremlins did it

Evolution: The Fossils Speak, but Hardly with One Voice


The thinking planet?

Earth's Biosphere Is Awash in Information