“Life Finds a Way”—Synthetic Minimal Cell Evolves to Recover Lost Fitness

A more recent and very different perspective is presented in Andreas Wagner’s 2015 book, Arrival of the Fittest: How Nature Innovates. I described the basic argument in this comment on 2023-02-28. The essence is that the calculations that Meyer and others present about the statistical improbability of even a moderate sized functional protein arising by random modifications to an existing protein sequence are based upon a linear organisation of amino acids in a chain (or, equivalently, codons in a DNA molecule). But when you arrange these one-dimensional strings into a multi-dimensional “protein space”, you find that due to the vastly higher dimensionality, each functional protein has enormously more neighbours which can be reached by a single unit replacement, and thus as many more pathways between structures which preserve functionality along the path. (From my comment):

The same experiment may be repeated on proteins, and one finds that starting with an 80 amino acid protein used to bind ATP and again changing just one amino acid at a time, there were 10^{93} equivalently functional proteins reachable from the starting point, all by a series of single residue changes of the kind a random mutation causes.

This means that as biology conducts its massively parallel search through the protein space, it is not constrained to having to leap directly from one functional protein from another, which might involve so many changes as to be statistically impossible, but is able to random walk from one very large region of functionality to another by single unit changes without ever losing functionality. Once arriving at a new basin of functionality, it can then explore further, increasing fitness in the new functionality, but now discarding the original functionality from which it originated.

Essentially, evolution defeats the combinatorial explosion of the number of possible proteins by its own combinatorial explosion of the number of variants of a given protein which retain its 3D folded functionality and a commensurate explosion in the number of pathways which can lead from one to another, all by just changing one amino acid or codon at a time.

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