Weekly poll: Replicators First vs. Metabolism First


I am preparing a class on the origins of life for next week. The textbook I am using does not  go into the Replicators First vs. Metabolism First argument, but I probably will, if I have time. Below, a quick refresher for those who know of the competing theories, and an unsatisfying introduction for those who don’t. In the end, you will ask to weigh the evidence and vote. Remember: your vote is important. I had a lousy week and seeing some numbers on the sidebar would be a nice ego-boost. Yes,  that lousy.

From Jarown's lab, NC State University http://www.mbio.ncsu.edu/JWB/soup.html

From James W. Brown's lab, NC State University http://www.mbio.ncsu.edu/JWB/soup.html

Replicators First

Aka RNA World: RNA emerges as the first molecule that can replicate and perform enzymatic processes. It stores information and it is biochemically active. Thus it can both replicate and control a primitive meabolism. Later came the transition to DNA as an information storage, and the enzymatic role was mostly relegated to proteins.The first replicators might not even have been RNA molecules, but some pre-RNA nucleic acid such as PNA or TNA.

This theory is supported by the present-day existence of ribozymes, RNA enzymes. Especially the ribozymic activity in the ribosome, the platform of protein translation. RNA can also catalyze its own replication, up to a certain length (189 bases was the longest self-replicating RNA synthesized in a lab).  Finally, RNA can also catalyze the formation of peptide bonds between amino-acids, setting the stage for the transition to an RNA+protein world. At some point, these reactions were cellularized by liposomes or other protobionts (pre-cellular structures with a protein, fatty or water boundary).

The arguments against the RNA World / Replicators First hypothesis are that RNA is labile, especially in water. Hence, an RNA world may not have been sustainable to become complex enough to recruit protein and bootstrap itself to the next level. Also, RNA is too complex to have been any kind of first player, and there were probably many chemical selective events prior to the appearance of RNA, as argued by the Metabolism First proponents.

Metabolism First

Metabolism First holds that metabolic processes assembled prior to the existence of replicators. Günter Wächtershäuser proposed that the pioneer organism originated in high (>100C) temperatures in hydrothermal vents.  This organism resembled the catalytic converter in a car, more than a primitive cell: it had a composite structure of a mineral base with catalytic transition metal centers, such as iron-sulfide and nickel-sulfide. Dissolved volcanic gases would flow over this natural catalytic converter, yielding more complex compounds. Some of those more complex compounds would stick around, and incrementally form more complex molecules, eventually capable of catalysis. Once strong experimental evidence in favor of Metabolism First is the ability to recreate most of the Citric Acid cycle — both universal and essential in all life — without enzymes, and in high temperature and pressure conditions, such as those existing in underwater volcanic vents, favored for being the crucible of life.
Information bearing molecules like nucleic acids, came last, rather than first. Metabolism First explains the chemical evolution of catalytic versatility before the appearance of complex polymers. Also, the argument made by Metabolism First proponents is that  RNA  itself is a precondition, but a molecule too complex to have arisen by initial chemical selection. Metabolism First offers the necessary chemical scaffolding enabling replicators to appear on the stage.

RNA First vs. Metabolism First

Replicators (genetics) First vs. Metabolism First. Barbara Aulicino and Morgan Ryan

There is a lot more to the two hypotheses, of course. Including experimental evidence supporting both. Here are two reviews. Read them, and don’t forget to cast your vote here → →

In support of Metabolism First:

Trefil, J., Morowitz, H., & Smith, E. (2009). The Origin of Life American Scientist, 97 (3) DOI: 10.1511/2009.78.206

In support of the RNA World (Replicators first):

Müller, U. (2006). Re-creating an RNA world Cellular and Molecular Life Sciences, 63 (11), 1278-1293 DOI: 10.1007/s00018-006-6047-1

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2 Responses to “Weekly poll: Replicators First vs. Metabolism First”

  1. david w says:


    I voted for metobolism first, but I wouldn’t put a lot of money on it.

    My completely chemistry-knowledge free intuition is that it’s more likely RNA or any RNA precursors arose from “chemical selection” rather than ‘plain old’ organic chemistry. The other interesting question is where did the invention of cells fit in…

  2. Fischer says:

    Metabolism first.
    Specifically it started with redox-active hydrocarbons dissolved in primitive membranes derived from amphiphilic compounds in meteorites.
    There you are. 😉