Search
  • Rob Stadler

Natural Processes Don't Make Biopolymers




If purely natural processes produced the first living organism, natural processes must have conveniently strung together perfect sequences of monomers (i.e., the basic building blocks of life: amino acids, nucleotides, lipids, and sugars) to form the essential biopolymers of life: RNA, DNA, proteins, and glycans. Thankfully, we know enough about natural processes to provide a definitive answer to this hypothesis.


This topic is addressed in the second origin-of-life video from the Long Story Short animated video series. We start by assuming that nature could form the monomers out of simpler molecules, select them out of a morass of other harmful and undesired molecules, concentrate them in one location, and accomplish this faster than the natural degradation of the monomers. A natural process to form biopolymers must then overcome several additional barriers.


The Water Paradox

Formation of biopolymers requires chemical interaction of the monomers, which requires some type of solvent. Because all existing life requires water as a solvent, Occam's razor compels us to first consider water. But chemistry makes it clear that water inhibits the polymerization of nucleotides, amino acids, and sugars to produce DNA, RNA, proteins and glycans, because water is produced during polymerization. More specifically, the natural process known as Le Chatelier’s principle dictates that monomers in water will remain monomers rather than form biopolymers. Living organisms must consume energy to produce biopolymers - the energy consumption is necessary to overcome the natural tendency for monomers to remain monomers. Just like cars do not naturally roll uphill, biopolymers do not naturally form in water. Also, water actively degrades biopolymers. For example, water damages DNA via deamination and depurination. In a typical human cell, it has been estimated that 2,000-10,000 depurinations of DNA occur every day.[1,2]


Some have attempted to sidestep the water paradox by suggesting wet/dry cycles or a different solvent facilitated the formation of biopolymers. However, we know that wet/dry cycles actually damage nucleotides by detaching nucleobases.[3] Wet/dry cycles also cause denaturation of proteins because water (i.e., a hydration shell) is necessary to maintain the critical 3-D structure of proteins. Replacing water with another solvent just adds another required layer of complexity - that of switching the solvent to water later in the progression toward life. And, there is no known mechanism to produce convenient pools of alternative solvents like formamide on the Earth.[4] Therefore, the observation that life consists of many complex biopolymers, with water as a solvent, is inconsistent with naturalistic expectations.


Homochirality

Another strikingly unnatural property of all biopolymers is homochirality. DNA, RNA, proteins and glycans are exquisitely sensitive to consistent chirality of all constituent monomers. We know that natural processes to produce chiral molecules strongly favor racemic mixtures - equal distributions of the chiral forms. If biopolymers were formed by purely natural processes, we should therefore expect their monomer constituents to be a racemic mixture. But what we observe is the extreme opposite - perfect consistency of chirality in all the biopolymers in all of life. And homochirality is not just a question of selecting the correct chiral form out of two possibilities - ribonucleotides have 16 different chiralities and sugars like sucrose have 512 different chiralities. It is hard to imagine a more unnatural configuration than the observed homochirality of life.


Scientists have been searching for prebiotically plausible natural processes that could produce homochirality. The most promising technique thus far is the well-known Soai reaction, published in 1995.[5] However, this technique requires dialkyl zinc chemistry with extreme purity and toxic solvents like toluene[6] - certainly not prebiotic conditions. In the 26 years since the Soai reaction was discovered, origin-of-life researchers have been searching for a way to increase its relevance. Donna Blackmond, an expert on chirality, recently stated: “A lot of people (our group included) are trying to find more prebiotically relevant reactions that could do what the Soai reaction does. So far, we haven’t been able to find one. So that’s kind of a holy grail.”[7]


Again, science provides a clear expectation of what natural processes produce, and what we observe in the biopolymers of life is dramatically unexpected.


Homolinkage

Another strikingly unnatural property of biopolymers is homolinkage - perfectly consistent bonding between the monomers. Every biology textbook depicts the familiar double helix structure of DNA. This produces the false impression that the double helix structure is the preferred way for the components to align naturally. In reality, the monomers can bond with each other in a large variety of ways and unwanted molecules can interfere with the required purity. Even in a very short DNA of just two nucleotides, there are dozens of incorrect possible arrangements of the components, and only one correct arrangement. The probability of consistent arrangement decreases exponentially as the DNA lengthens. If natural processes could polymerize these monomers, the result would be chaotic “asphalt”, not highly organized, perfectly consistent biopolymers. Think about it – if monomers spontaneously polymerized within cells, the cell would die because all monomers would be combined into useless random arrangements.


Scientists have been trying for decades to get monomers to link up into biopolymers under “prebiotically plausible conditions”. Back in 1993, they produced chains of nucleotides up to 11 monomers in length, although ⅓ of the phosphodiester bonds were incorrect.[8] Thirteen years later, they claimed to produce chains with up to 50 nucleotides.[9] Unfortunately, the latter claims were not reproducible because their measurement technique couldn't separate true polymers from aggregates of separate molecules.[10] Whether scientists can produce chains of 11 or 50 monomers is of little relevance, because the simplest known forms of autonomously reproducing life have more than 500,000 base pairs of DNA with perfectly consistent linkage of components. According to what we know about natural laws, the biopolymers of life are extraordinarily unnatural.


Natural Degradation and Required Repair of RNA and DNA

RNA is hypothesized to have preceded DNA, replicating itself and growing in complexity over millions of years toward the origin of life. But these expectations clearly contradict what we know about natural laws. Anyone who works with RNA knows that it is an extremely fragile molecule that degrades in a matter of hours at room temperature, even in the absence of RNases. RNA is best preserved as a precipitate in ethanol, stored at -70 degrees C, and protected from light.[11] Also, a true self-replicating RNA has never been observed. Some propose that small peptides or RNA loops helped to stabilize the RNA, but these same factors would further confound the possibility of RNA replication.


If natural processes could produce a lengthy molecule of DNA or RNA, complex repair mechanisms would be required to preserve the information content. Fortunately, all living things are equipped with complex enzymatic repair mechanisms. Unfortunately, the information to produce these repair mechanisms must be stored within the DNA/RNA. But the information in the DNA/RNA can’t be maintained without the repair mechanisms. So, you can’t have long strands of DNA/RNA unless it can repair itself. But it can’t repair itself unless you have long strands of DNA/RNA.This is Eigen’s Paradox: a chicken-and-egg problem that has been around, without a solution, for 50 years.[12]


Summary

If purely natural processes started the first life, complex biopolymers like RNA, DNA, proteins, and glycans must have formed naturally. But we know enough about the natural laws that govern chemical and biochemical reactions to know better. The essential presence of long, homochiral, homolinked biopolymers in a water solution, for all known life forms, is astoundingly unnatural. It has been 70 years since the Miller-Urey experiment produced amino acids. At that time, we didn’t even know the structure of DNA. In the last 70 years, we have learned a great deal about the extremely unnatural properties of biopolymers, which explains why almost no discernable progress has been made toward producing biopolymers via prebiotic processes in laboratories.


1. Lindahl T. Instability and decay of the primary structure of DNA. Nature, 1993. 362: 709–715.

2. Lindahl T, Nyberg B. Rate of depurination of native deoxyribonucleic acid. Biochemistry, 1972. 11: 3610–3618.

3. Mungi CV, Bapat NV, Hongo Y, Rajamani S. Formation of abasic oligomers in nonenzymatic polymerization of canonical nucleotides. Life 2019; 9, 57; doi:10.3390/life9030057

4. Zachary AR, Hongo Y, Cleaves HJ II, Yi R, Fahrenbach AC, Yoda I, Aono M. Estimating the capacity for production of formamide by radioactive minerals on the prebiotic Earth. Scientific Reports 2018. 8: 265.

5. Soai, K., et al., Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule. Nature, 1995. 378(6559): 767–768.

6. Gehring T, Busch M, Schlageter M, Weingand D. A Concise Summary of Experimental Facts About the Soai Reaction. Chirality, 2010. 22: E173–E182.

7. https://www.youtube.com/watch?v=tGTVZ78JLi8 25:55 Feb, 2021.

8. Ferris, J. P. and G. Ertem, Montmorillonite catalysis of RNA oligomer formation in aqueous solution. A model for the prebiotic formation of RNA. J Am Chem Soc, 1993. 115: 12270–12275.

9. Huang, W. and J. P. Ferris, One-step, regioselective synthesis of up to 50-mers of RNA oligomers by montmorillonite catalysis. J Am Chem Soc, 2006. 128(27): 8914–8919.

10. Burcar BT, Cassidy LM, Moriarty EM, Joshi PC, Coari KM, McGown LB. Potential Pitfalls in MALDI-TOF MS Analysis of Abiotically Synthesized RNA Oligonucleotides. Origins of Life and Evolution of Biospheres, 2013. 43: 247–261.

11. https://lifescience.roche.com/en_us/articles/precautions-for-handling-of-rna.html

12. Eigen M. Selforganization of matter and evolution of biological Macromolecules. Naturwissenschaften, 1971. 58: 465–523.

3 views0 comments