Complex Experimental Autocatalytic Sets

Autocatalytic sets are self-sustaining chemical reaction networks which are believed to have played an important role in the origin of life, and to be an underlying principle of living systems in general. They have been studied in great detail both mathematically and with computer simulations, and actual experimental examples have been constructed in the lab. However, so far these experimental examples were of a limited complexity (so-called “elementary” autocatalytic sets). Recently, though, a group of researchers have constructed and studied the first experimental example of a more complex (“non-elementary”) autocatalytic set.

An autocatalytic set is a self-sustaining reaction network in which all molecules mutually catalyze each other’s formation from a basic food source. More specifically, an autocatalytic set is a set of molecules and the chemical reaction between them such that each reaction is catalyzed by at least one of the molecules from the set, and each molecule can be produced from a basic food source through a sequence of reactions from the set itself. A simple example is given in the figure below, with molecule types \(f_1,\ldots,f_5\) comprising the food set, and \(p_1,\ldots,p_4\) being the catalysts. Autocatalytic sets are believed to have played an important role in the origin and early evolution of life.

A simple example of an autocatalytic set. Dots represent molecule types, boxes represent chemical reactions. Dashed arrows indicate catalysis.

Several examples of autocatalytic sets have been constructed experimentally in the lab, most notably a set of nine peptides, and a set of 16 ribozymes (catalytic RNA molecules). However, all these existing experimental examples are of the kind we have recently called elementary autocatalytic sets : all catalysts are created directly from the food set, each needing only one reaction step. Of course these are still perfectly fine examples of autocatalytic sets, and allow a convenient linear algebra analysis to be applied (in particular the calculation of eigenvalues and eigenvectors), but they lack real biological complexity, where catalysts generally require multiple reaction steps to be produced from the food set.

Recently, though, a group of researchers in Paris, France, have constructed a more complex autocatalytic set, where the catalysts do indeed need multiple reaction steps to be formed from the food set, with all these intermediate steps being catalyzed by the eventual products. They did this by using the original 16-ribozyme experimental example, and modifying some of the RNA fragments in the food set, such that these molecules first need to be broken down into smaller fragments (a catabolic process) before they can be combined (an anabolic process) into the final products, i.e., the catalysts. A schematic example, taken from their recently published paper, is shown in the figure below.

Left: The original system, with only one anabolic reaction step. Right: The modified system combining several catabolic reation steps with one anabolic reaction step. Grey arrows indicate catalysis. Reproduced from Arsène et al., NAR, 2018.

With this, another important step forward has been made in the experimental study of autocatalytic sets, making them ever more plausible candidates for a possible origin of life scenario. I’m curious to see what else will come out of this Paris lab!