Protocells, the origins of life, and the RNA World

This essay is a bit less formal than many I’ve posted here, more of an indulgence than the cut-and-dried stuff I’ve been posting about polyadenylation. It is essentially a repost of an essay I posted on the old ARN boards many years ago. I’m moved to this by a recent a recent article in PNAS. The overall context is the origin of life, and some of the different arguments and perspectives that are brought to the table in ev/cre debates.

As a segue, the abstract of the PNAS article:

“Life is that which replicates and evolves. The origin of life is also the origin of evolution. A fundamental question is when do chemical kinetics become evolutionary dynamics? Here, we formulate a general mathematical theory for the origin of evolution. All known life on earth is based on biological polymers, which act as information carriers and catalysts. Therefore, any theory for the origin of life must address the emergence of such a system. We describe prelife as an alphabet of active monomers that form random polymers. Prelife is a generative system that can produce information. Prevolutionary dynamics have selection and mutation, but no replication. Life marches in with the ability of replication: Polymers act as templates for their own reproduction. Prelife is a scaffold that builds life. Yet, there is competition between life and prelife. There is a phase transition: If the effective replication rate exceeds a critical value, then life outcompetes prelife. Replication is not a prerequisite for selection, but instead, there can be selection for replication. Mutation leads to an error threshold between life and prelife.”

Now, I’m not saying that I have been saying exactly these things. But I think that ideas outlined in the following would seem to be finding renewed interest. The old essay follows – I have left in the old ARN-style formatting, so that there is no question about revisions. This may make for a tiny bit of confusion. But that’s my choice here. As always, enjoy.
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Back in this thread [I apologize – the link was dead, so I have omitted it], jazzraptor asked some interesting questions regarding Fox’s protocells and the RNA World. I haven’t any answers, but some comments that show how the perspective of an ID critic may add new ideas to this matter.

Jazzraptor said:

Hi Art:

I’m not arguing that abiogenesis is impossible, exactly. I’m going to try to view the broad subject without dogma of any sort (though perhaps that IS impossible!) RBH implicitly asked chiral kid, “why the incredulity?” I nosed in and provided four considerations to the thread that pump up my incredulity. Fox’s protocells are what they are, and their existence indeed supports the case that abiogenesis may be possible.

So let’s assume that life did start with these pre-life forms. How do the protocells incorporate RNAs? The protocells require a specific environment. Is this environment RNA World friendly

Good questions all. For the sake of review, let’s recall some properties of protocells (culled from the above-cited thread – sorry for being lazy in this). They display:

electrotactism (the ability to sense an electrical field)

aggregation (the ability to collect into colonies)

mobility (the ability to move more or less at will)

osmosis (the ability to absorb material from the environment)

permselectivity (the ability to selectively pass materials across a semi-permiable barrier)

fission (the ability to break about into smaller functional units)

reproduction (the ability to create functional copies)

conjugation (the ability to join directly to another)

communication (the ability to pass information directly to another)

excitability (the ability to generate and utilize energy, especially electrical fields)

In addition, “(p)roteinoids or proteinoid microspheres have many activities. Esterolyis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities.” (From the review by Nakashima.)

Ask a high school bio student (e.g., perform a sort of “toddler test”) if these characteristics would qualify something as being alive, and the answer very likely would be yes. But in spite of this, OOL research has largely (but not entirely) moved on from these “creatures”. Why is this, if we are so close to (or even at) the point of having created cellular life from little more than amino acids? The answer is simple – there isn’t a very good conceptual link between protocells and life as we know it – e.g., the “DNA+RNA+protein” world. (Apologies to those who have more lipophilic or glycophilic perspectives.) In particular, it hasn’t been easy to see how a durable genetic system, based on DNA or RNA, can have developed from a stable protocell-based ecosystem.

By most accounts, the RNA World hypothesis affords a better framework in which the origination of nucleic acid-based genetic systems might be studied. Briefly, this is because a big conceptual difficulty – linking replication with a coding capacity for catalytic moieties – is seamlessly solved with the realization that RNAs can be catalytic as well as informational. The RNA World also provides interesting insight into the nature of many, many properties of living cells – that polypeptide biosynthesis is catalyzed by RNA, that RNA processing is largely an RNA-catalyzed process, that RNAs large and small can mold and shape the form and function of chromosomes, the curious similarities between RNA viruses and parts of the translational system, etc., etc. Viewed in this light, the many roles that RNA play in living things are viewed as vestiges of an ancient RNA or RNA+protein world. For these (and many other) reasons, OOL research has moved on, with Fox’s work having been filed (for now – we’ll see that some enterprising soul will likely revive some similar idea, with the possibility of very exciting results).

But there’s something missing from these musing. Ribosomal RNA, RNAse P (the RNA part), the RNA component of telomerases, and other functional (as opposed to structural or scaffold) RNAs are supposed to represent ancient activities that were solely RNA-based. This raises a question – where’s the RNA component of replicases in extant life? If the RNA catalyst for, say, polypeptide synthesis has persisted for 3 billion+ years, then why has not the central RNA core of the primordial replicases also persisted? The easy answer is that other protein-based catalysts that arose later were better and probably supplanted the RNA-based replicases. But there’s a more provocative answer that an ID critic’s perspective can give.

Recall, now, one of the failed predictions of ID – that the information content of functional macromolecules would be high, enough so as to support some sort of design inference. As a matter of fact, direct experimental measurements as well as the success of bioinformatics tools for identifying function in newly-sequenced genes tell us that the informational content of proteins is inherently low. From a practical perspective, this means that any sizeable population of randomly-assembled chains of L-amino acids will likely have a large, diverse range of catalytic activities. As indicated by Nakashima (above), this will also hold for thermal proteins and their protocell products, entities that could readily (probably copiously) form in prebiotic conditions. And, as indicated in Nakashima’s review, one such property would include the ability to synthesize oligonucleotides.

This realization brings us to a proposal that is rather different (to my knowledge – I haven’t kept up with the more theoretical or abstract OOL literature, and would welcome corrections to my claims of novelty) from most that are discussed. Specifically, it is possible that the first RNA replicase was not an RNA, but rather a conglomeration of protocells. (The concept of a population of “enzymes” is important here. This is a viable suggestion – if one takes the frequency of occurrence of simple nucleotidyltransferase to be on the order of 1 oligomer in 10^14, the size of an average thermal protein to be about 10^4 g/mole, and the thermal protein content of an average protocell to be about 10^-13 g [protocells are roghly the size of a run-of-the mill bacterial cell], then one can calculate that a population of 10^7 protocells will contain at least one polymerase. Put another way, 1 gram’s worth of protocells would possess a million different polymerases. In round numbers, of course.)

What is interesting about this proposal (IMVHO ) is that it eliminates the need for a reproducing RNA polymerase at the outset of abiogenesis – such enzymatic activities would occur often enough in any steady-state population of protocells that they would always be present. Thus, a stable and evolving population of RNAs (which would themselves include all matter of catalytically active or otherwise functional molecules) could arise and persist without the initial appearance of the RNA-based catalyst needed to produce such a population.

This post is already too long, but it should be easy to see how such an initial system, coupled with processes that are suspiciously Darwinian in their actions, could provide both a beginning and stepping stones towards a more recognizable RNA+Protein World. The main point is that the perspective afforded by one failure of ID theory provides a new and interesting hypothesis for the beginnings of life as we know it (as opposed to just life).

[edited to fix a really ugly piece of grammar. Probably needs more ]
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The review by Nakashima mentioned above:

Top Curr Chem 1987;139:58-81

Metabolism of proteinoid microspheres.
Nakashima T.
Institute for Molecular and Cellular Evolution, University of Miami, Coral Gables, Florida, USA.
The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolyis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

The pertinent details for the PNAS article:

Mark Nowak and Hisashi Ohtsuki, 2008, Prevolutionary dynamics and the origin of evolution, PNAS 105, 14924-1492.