Could life have started with Simplicity?

One of the perplexing questions people ask in the origin of Life is how did such complexity ever evolve from a simple broth of chemicals in the prebiotic world. The first person to ever attempt to try to answer it was Harold Urey and Stanley Miller who created a chemical soup of ammonia (reduced Nitrogen), methane (reduced C), and hydrogen (should be present in a reduced atmosphere) and subjected the soup to electric discharge (simulating lightning and solar radiation). This experiment was performed in the 1950s and was done to simulate early Earth condition. After this electric discharge passed through the soup, simple amino acids and sugars and the raw materials for nucleic acid bases such as adenine were found to be created in this mixture [1]. These are all the raw ingredients for biochemistry to start hence bringing evolution of the origin of life into the realm of experimental science for the first time. Even though, the conditions of early Earth have come into question since then, Urey and Miller deservedly received a Nobel prize for the novel aspect of their work. In fact, the experiments were repeated recently with nitrogen gas instead of ammonia, carbon dioxide instead of methane, and hydrogen or water (currently accepted conditions for early Earth), and the products from the broth were similar in nature to those found in the Urey-Miller experiment.

In the prebiotic world envisioned by most scientists, chemistry would have dominated the changing scenario and landscape found in Earth. Chemistry, unlike biochemistry, is very non-specific and would create a huge pool of chemicals. Under the assumption that there were signs of modern cellular organisms in that pool (and this is a big assumption made out of necessity), then all or most of the biochemical reactions would be a small subset of all the reactions occurring in this pool called protometabolism [2]. Somehow, after the first catalyst were formed (not as efficient as modern enzymes), those catalysts were more specific towards a subset of these reactions and made these reactions occur at a faster rate leading to a feedback mechanism by which these reactions became the dominant reactions leading to the biochemicals or life as we know it now.

One such theory of the origin of life states that an autocatalytic reaction cycle was present in the chemical gemisch in the prebiotic world and by the nature of it being autocatalytic, it started dominating this prebiotic world leading to the first signs of life [3-6]. One such autocatalytic cycle is the tricarboxylic acid cycle (TCA or Krebs or Calvin cycle), which is present in all modern organisms in one form or the other [7]. The TCA cycle is the only route of carbon fixation into biochemicals starting with carbon dioxide as the source of carbon [8,9]. In one form of the cycle, called the reverse TCA cycle (and found in few organisms), the overall reaction can be visualized as 2 molecules of carbon dioxide (found in prebiotic earth) reacting with a molecule of citrate and 6 molecules of hydrogen to form 2 molecules of citrate and 5 molecules of water. The important thing to note is that 2 molecules of citrate were formed from 1 molecule of citrate hence producing more of the reactant. In other words, 2 molecules of citrate can be used as reactant in the next round of the TCA and the cycle is hence called autocatalytic. As it is autocatalytic, once prebiotic conditions existed where this cycle could take place completely (all reactions in it have to take place), this cycle would have taken place much faster after some time and would have slowly dominated the early prebiotic metabolism.

In addition, in modern cells, the TCA or the rTCA cycle is at the center of a cell's metabolism. In other words, the intermediates of the TCA cycle form amino acids, nucleotides, and cofactors for the rest of the cellular machinery. So, after this cycle starts to dominate the prebiotic world, the side reactions would start producing amino acids and nucleotides leading to complexity required for biochemistry to begin [8]. However, the conditions required for this cycle to take place completely have not been found so far. Secondly, the source of energy of these reactions and the compartmentalization of these reactions (to cause insignificantly higher concentration of these biochemicals) is still a matter of speculation and further research.

It was postulated that in early prebiotic conditions, these reactions could have taken place on clay or on metal sulfide surfaces such as FeS. These metals would have themselves been oxidized to ferric sulfide providing energy to take place to completion [3,4]. Another theory is that it may not have been just the TCA cycle but some other cycle like the ribose cycle that could have been at the origin of metabolism [5]. The advantage of the ribose cycle is that unlike the TCA cycle, there are only 1 or 2 reactions in the cycle that do not take place at an appreciable rate without a catalyst and hence only 1 or 2 reactions need the clay or metal surface as a catalyst.

In either case, it is a question whether an autocatalytic cycle should be considered as life. In my opinion it should not, even though it is producing more of itself (chemical form of reproduction) at the end of the day and there is energy conversion in the cycle (metabolism). It is just that life is very specific and driven unlike early chemistry which would have been highly aspecific. But this is certainly a matter of speculation and discussion.

[1] Biochemistry - Stryer.
[2] Singularities - de Duve.
[3] Wechterheuser - Evolution of the first metabolic cycles - PNAS, 87:200-204, 1990.
[4] Wechterheuser - On the chemistry and evolution of the pioneer organism - Chemistry and Biodiversity, 4:584-602, 2007.
[5] Orgel - Self-organizing biochemical cycles - PNAS, 97:12503-12507, 2000.
[6] Smith and Morowitz - Universality in intermediary metabolism - PNAS, 101:13168-13173, 2004.
[7] Wikipedia entry on Citric acid cycle.
[8] Morowitz, Kostelnik, Yang, and Cody - The origin of intermediary metabolism - PNAS, 97:7704-7708, 2000.
[9] Srinivasan and Morowitz - Ancient genes in contemporary persistent microbial pathogens - Biol. Bull., 210:1-9, 2006.

PS: Stanley Miller passed away this year at the age of 77 and this post is dedicated to him.