Structure of RNA

The structure of the RNA for the large ribosomal subunit in E. Coli. (About 3000 nucleotides.) The ribosome also has a small RNA sub unit (~1500 nt) and about 50 proteins. A happy accident?
We address the following hypothesis: If purely natural processes produced the first living organism, such 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.

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. (An earlier Long Story Short episode on the origin of life clearly refuted these assumptions.) 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, 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 of monomers to remain monomers. Just as 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 that 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.

The Homochirality of Biopolymers

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.
molecule chirality
© Donna Blackmond
Examples of molecular chirality
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 toluene6 — 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.

Long Story Short: Polymerization

Rob Stadler received a PhD from the Harvard/MIT Division of Health Sciences and Technology. As a scientist in the medical device industry, he has obtained 150 US patents and has contributed to devices that are implanted in millions of patients with heart disease. Rob is author of The Scientific Approach to Evolution: What They Didn't Teach You in Biology and co-author of The Stairway to Life: An Origin-of-Life Reality Check.
  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. 25:55 Feb, 2021.