Saturday, May 16, 2020

Origin of Life- RNA Only, or Proteins Too?

Proteins as Participants in the Origin of Life

After going through some momentous epochs in the history of life in the last two weeks (the origin of eukaryotes, and the nature of the original metabolism), we are only part of the way to the origin of life itself. The last common ancestor of all life, (LUCA), rooted at the divergence between bacteria and archaea, was a fully fledged cell, with many genes, a replication system and translation system, membranes, and a robust metabolism based on a putative locale at hydrothermal vents. This is a stage long after the origination of life, about which our concepts remain far hazier, at the chemical interface of early Earth.

A recent paper (and prior) takes a few more speculative shots at this question, (invoking what it calls the initial Darwinian ancestor, or IDA), making the observation that proteins are probably as fundamental as RNA to this origination event. One popular model has been the "RNA world", based on the discovery that RNA has some catalytic capability, making it in principle capable of being the Ur-genetic code as well as the Ur-enzyme that replicated that same code into active, catalytic molecules, i.e., itself. But not only has such a polymathic molecule been impossible to construct in the lab, the theory is also problematic.

Firstly, RNA has some catalytic ability, but not nearly as much as it needs to make a running start at evolution. Second, there is a great symmetry in the mechanisms of life- proteins make RNA and other nucleic acids, as polymerases, while RNA makes proteins, via the great machine of the ribosome. This seems like a deep truth and reflection of our origins. It is probable that proteins would, in theory, be quite capable of forming the ribosomal core machinery- and much more efficiently- with the exception of the tRNA codon interpretation system that interacts closely with the mRNA template. But they haven't and don't. We have ended up with a byzantine and inefficient ribosome, which centers on an RNA-based catalytic mechanism and soaks up a huge proportion of cellular resources, due to what looks like a historical event of great significance. In a similar vein, the authors also find it hard to understand how, if RNA had managed to replicate itself in a fully RNA-based world, how it managed to hand off those functions to proteins later on, when the translation function never was. (It is worth noting that the spliceosome is another RNA-based machine that is large and inefficient.)

The basic pathways of information in biology. We are currently under siege by an organism that uses an RNA-dependent RNA polymerase to make, not nonsense RNA, but copies of itself and other messages by which it blows apart our lung cells. Reverse transcriptases, copying RNA into DNA, characterize retro-viruses like HIV, which burrow into our genomes.

This thinking leads to a modified version of the RNA world concept, suggesting that RNA is not sufficient by itself, though it was clearly central. It also leads to questions about nascent systems for making proteins. The ribosome has an active site that lines up three tRNAs in a production line over the mRNA template, so that the amino acids attached on their other ends can be lined up likewise and progressively linked into a protein chain. One can imagine this process originating in much simpler RNA-amino acid complexes that were lined up haphazardly on short RNA templates to make tiny proteins, given conducive chemical conditions. (Though conditions may not have been very conducive.) Even a slight bias in the coding for these peptides would have led to a selective cycle that increased fidelity, assuming that the products provided some function, however marginal. This is far from making a polymerase for RNA, however, so the origin and propagation mechanisms for the RNA remain open.

"The second important demonstration will be that a short peptide is able to act as an RNA-dependent RNA polymerase."
- The authors, making in passing what is a rather demanding statement.

The point is that at the inception of life, to have any hope of achieving the overall cycle of selection going between an information store and some function which it embodies or encodes, proteins, however short, need to participate as functional components, and products of encoding, founding a cycle that remains at the heart of life today. The fact that RNA has any catalytic ability at all is a testament to the general promiscuity of chemistry- that tinkering tends to be rewarded. Proteins, even in exceedingly short forms, provide a far greater, and code-able, chemical functionality that is not available from either RNA (poor chemical functionality) or ambient minerals (which have important, but also limited, chemical functionality, and are difficult to envision as useful in polymeric, coded form). Very little of the relevant early chemistries needed to be coded originally, however. The early setting of life seems to have been rich with chemical energy and diverse minerals and carbon compounds, so the trick was to unite a simplest possible code with simple coded functions. Unfortunately, despite decades of work and thought, the nature of this system, or even a firm idea of what would be minimally required, remains a work in progress.


  • Thus, god did it.
  • Health care workers can be asymptomatic, and keep spreading virus over a week after symptoms abate.
  • Choir practices are a spreading setting.

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