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Making the Jump from Prelife to Life: The Enigma Remains

achre4.2012.45.issue-12.cover.jpgThe American Chemical Society's special issue of Accounts of Chemical Research is dedicated to chemical evolution. See our previous comments here and here. Now let's look at an article by Irene Chen and Martin Nowak that addresses the fundamental evolutionary step involved in making the transition from non-life to life ("From Prelife to Life: How Chemical Kinetics Become Evolutionary Dynamics"). The authors say that they are going to explain how longer RNA sequences arise from shorter ones and how the ability to replicate emerges.

OK, let's hear it.

Well, the article proposes a model based on prior origin-of-life research. Thus the authors assume that certain research questions are already answered. Many of their assumptions are, however, problem areas for RNA-world experiments.

The model on offer is based on chemical kinetics (reaction rates) giving rise to evolutionary dynamics (replication and competition). Essentially, the authors define "prelife" as a system that maintains chemical rules and "life" as a system that maintains biological rules. Prelife systems are subject to chemical equilibrium and reaction rates. Living systems are subject to environmental pressures and replication rates. Therefore, the point at which a chemical system can self-replicate is the point at which the system transitions from prelife to life. Here is how the authors define this distinction:

Prelife is characterized by gentle changes in the abundance of different sequences in response to differences in reactivity. Such a response of the system would be familiar to those who study chemical systems. On the other hand, if the polymers are able to template and thereby self-replicate, the dynamics change abruptly, and the fittest sequences dominate the pool in large excess even if they are only slightly better replicators than the rest. And if two systems compete for resources, one can exclude the other. Such features would be familiar to those who study biological systems.
Implicit here is the assumption that biological and chemical systems operate differently. But the authors explicitly compare their model to a bottom-up approach to synthetic life. Usually when people take a "bottom-up" approach, they are assuming that biology is reducible to chemistry. Otherwise it is NOT a "bottom-up" approach, but is based on some other overarching parameter or driving force.

Here is a summary of the proposed model:

Monomers react to form polymers (this is a polymerization reaction), and monomers keep adding to polymers to make longer polymers. Monomers may also add to other monomers to make short polymers. Soon, there is a sea of polymers with varying components. In RNA, these would be different nucleotide sequences. You also have polymers with varying lengths within this sea of "options." Now the polymerization reactions occurring in this sea are occurring at different reaction rates based on length and sequence. The faster reactions are going to occur more frequently and, therefore, will make more of the polymer products that came from the reactants that have the fastest reactions.

This, of course, is a thought experiment, so it is based on conjecture, but it makes sense only as long as we assume that we have somehow formulated just the right circumstances for these polymerization reactions to occur. According to the authors, we must also assume that fragments and bi-products are removed from the system, somehow. They do not specify how.

They go on: "Let us now suppose that some prelife sequences have the ability of replication." The authors set out originally to explain how replication arises, but when you read the article, there is no explanation of how exactly it did arise. Their example illustrating this ability to replicate doesn't help all that much (emphasis added):

For example, at an early stage of the development of the RNA world, many possible nucleobases would have coexisted. But not all of these nucleobases could support templating, which is required for replication. Some sequences would happen to contain nucleobases that could template a complementary strand...
From this point, the authors discuss competition based on replication rates, which assumes that some strands are capable of templating, somehow. Once replication is possible, then evolutionary pressures are in play, and we have made the transition from prelife to life. Their explanation of why the nucleotides, A, U, C, and G, and the ribose backbone are selected over other options is a bit circular:
The ability to replicate nonenzymatically would give a tremendous advantage to a templating polymer, even given a disadvantage of decreased chemical stability. Nucleobases that were poor for templating would be eliminated as sequences containing them lost the competition, effectively selecting for a nucleobase system that best supported base pairing and replication. Later takeovers could happen as even better replicators arose, ultimately resulting in RNA.
In other words, the nucleobases were selected because they happen to allow for template-directed replication, but we still have no idea how or why template-directed replication even arose in a pool of polymers of varying monomer identity and lengths. The authors have successfully appealed to chance to explain what they set out to explain, and covered for their assumptions by referencing articles that conducted those studies, without addressing some of the problems with those studies.

In the introduction to their article, Chen and Nowak describe the transition from non-life to life as a seemingly "impossible leap because so many transitions must occur to transform the jittery molecules into a living structure." Their solution to this problem is to break down the origin of life into smaller and smaller transitions and "look for simple ways that physical and chemical effects could accomplish each transition."

The problem is there is not a simple way to construct a cell, or a protocell, or a replicating RNA strand, let alone one with a meaningful sequence. No matter how small you slice the steps, there are still biologically (and chemically) impossible leaps from one slice to another and another. Can this enigma be resolved? Unfortunately, the effort represented in this article will not suffice to do so.