Metabolic Evolution

Evolution is messy. The evolution of metabolic pathways is murky because different observations have led to different hypothetical models to explain how things work. Can these different hypotheses be tested? Possibly, at least that’s the subject of a paper titled “In Silico Evolution of Early Metabolism” (Artificial Life 2011, 17, 87-108). The authors and abstract are shown below.

Four scenarios are considered.

(1) In the backward evolution hypothesis, enzymes further downstream in extant biochemistry are evolutionarily older. This seems counter-intuitive at first glance, but makes sense because one might expect early autocatalytic cycles to deplete a chemical ‘food’ source, and therefore the system evolves to make new molecules as alternative inputs to the system.

(2) In the forward evolution hypothesis, the opposite is expected – evolutionarily older enzymes should be upstream. The idea is that evolution proceeds by building on increasingly available intermediate molecules generated from earlier catalytic steps. Demand is generated from production, so to speak.

(3) In the patchwork model, new pathways co-opt enzymes from pre-existing pathways. Perhaps a mutation results in an enzyme becoming a better fit to catalyze an alternative useful reaction. Reuse the old for the new!

(4) In the shell hypothesis, metabolism grows first from an initial autocatalytic core and new ‘shells’ are constructed around this core. Hence, you’d expect to see highly conserved ‘ancient’ enzymes in the core and newer ones appearing in successive shells.

These scenarios are not mutually exclusive. The simulations in the paper lend support to different models/hypotheses depending on the variable ‘environmental’ conditions. For example, when food is abundant, forward evolution is observed, but when food is scarce, backward evolution begins to show up.

Two of the hypotheses were first proposed by Morowitz – I’ve blogged about his book Mayonnaise and the Origin of Life, and he has come up with some pithy definitions of life. Over the years I’ve found myself increasingly persuaded by some of his foundational ideas related to prebiotic chemistry, and my current sabbatical aims to explore some of these aspects. The challenge is that biochemistry is highly evolved, and even seemingly ancient enzymes and metabolic pathways have likely undergone much refinement over the millennia, by which I mean millions and millions of years. (Why on earth is a millennium a thousand years anyway?)

We can’t replay the tape (except maybe in a boardgame!) and hypotheses and models will continue to remain speculatory. Simulations can only take us so far, and by their very nature, simulations have to be highly constrained for the calculations to be tractable. Otherwise you might be waiting millennia for a great supercomputer to come up with answer for which the question might be ill-posed.

Evolution is messy. All proposed scenarios and more are likely contributors to the twists and turns leading to the constrained molecular diversity we observe in life today. I do think that ‘omnivorous eating’ is important in the chemical origins of life. In the quest for efficiency, metabolism has become increasingly specialized. A reduction of messiness perhaps, but managing the messy will always be an issue; perhaps that gives us a clue into the evolutionary process of metabolism!