What are the major principles that controlled the origin of life?
Singularities: Landmarks on the Pathways of Life
- Christian de Duve
Christian de Duve seeks to understand the mechanisms underlying the major changes that occur during the origin and history of living systems — the singularities. These include the origin of the protometabolism, membranes, protein, DNA and the prokaryote–eukaryote divide. He wants to know whether such transitions are necessary, almost inevitable, or very unlikely (even though they happened anyway). Are there alternatives that were essentially as good, or potentially better? Were the choices externally or internally imposed? And so on.
Singularities — the latest book to be tagged as de Duve's last — is in the tradition of The Major Transitions in Evolution by John Maynard Smith and Eörs Szathmáry (W. H. Freeman, 1995), which covered the aforementioned transitions but focused more on later stages, such as meiosis, multicellularity and language. Most of de Duve's book, in contrast, centres on the origin and nature of life, although he does go on a thoughtful scamper from the last universal common ancestor, the origin of eukaryotes, and multicellularity, before reaching the arrival of humans. Most of the book, then, is the great quest for the origin of life, next to which Frodo and Sam's journey into Mordor to destroy the Ring pales into a simple tourist trip.
De Duve poses a very important question: what are the fundamental issues that have to be 'solved' to get life as we know it? In evolutionary biology over the past few decades, we have mainly heard the 'contingency' message, which emphasizes the stochastic nature of evolution and focuses on the details. As we have heard countless times, if we rerun the tape of life again we will get something a bit different, and so on. Certainly, we are unlikely to get a horse-like creature with serine at position 23 of a β-haemoglobin, and a human-like animal with alanine at the equivalent position. But focusing only on contingency misses the more fundamental questions of major principles to which life might be conforming, and whether some general outcomes are predictable. This is the approach taken by de Duve.
As an example, consider Jeremy Knowles' view that an enzyme has catalytic perfection if it is limited by the rate of diffusion of a small substrate molecule onto the enzyme; no change to the properties of the enzyme can speed up the rate of the reaction. Because archaea, bacteria and eukaryotes can each have an equivalent enzyme that is 'perfect', but with very different protein sequences, there must be millions of different sequences that will carry out the reaction at the maximal speed. Now isn't this a much more fundamental and interesting conclusion than just that the sequences differ?
We can either concentrate on the principles, or we can focus on the details. Yes, the details will differ if the tape of life is rerun, but will we get the same basic metabolism and energy sources? Would we start again with RNA? Will we get proteins as the primary catalysts? Will there be a mix of primary producers, herbivores, carnivores and saprophytes, as well as small bacterial-like cells and larger-celled predators? Why do we not have endothermic plants? These are the big, interesting questions. De Duve focuses on these principles, refusing to be sidetracked by contingencies.
The view that de Duve argues is far more darwinian than many have used over the past few decades. Charles Darwin learned from the early statistical interpretations of Adolphe Quetelet that we could make firm predictions about random events if we had really large numbers. Even a rare event will be effectively certain to occur if there are millions of trials over millions of years. From this, you might gather that I like de Duve's contemplative approach. Yes, contingency and the stochastic nature of evolution are very important, but there is much more besides.
De Duve's general approach is fine, then, but how about the specifics? He favours a weak version of the RNA world in which most RNA catalysts are relatively short and are assisted by short (non-coded) peptides combined with other compounds that he calls multimers. It is unfortunate that we don't expect to find much evidence for such relics in modern metabolism — in contrast to cofactors (such as NADH and FAD), which are generally interpreted as relics of catalytic RNA from the RNA world. If there were such multimers, the amino-acid parts at least could be incorporated directly into the protein backbone of modern proteins, and therefore not be recognized as relics.
What are the next experiments? Are the chemical reactions that support life easier or harder at a pressure of hundreds or thousands of atmospheres? Are dilute or high concentrations advantageous? All life now occurs at high concentrations, restricted by membranes.
The biologists' top-down approach is making good progress in simplifying living systems to their basics. However, chemists seem to be having a harder time with their bottom-up approach.
The mathematics of Elchanan Mossel and Mike Steel argue that autocatalytic cycles, given relatively simple assumptions, are expected to occur in simple non-living systems. Experiments with in vitro RNA evolution are able to test many trillions of sequences simultaneously. Could chemists carry out trillions of reactions simultaneously? Perhaps the new approach of evolving proteins in oil droplets (Nature 440, 156–157; 2006) could be adapted?
Most of us, most of the time, are solving simpler problems in biology. But we should always be alert to the great problems, such as understanding the processes leading to the origin of life. Given past experience, such great questions will be solved — not by chance but by the prepared mind. This book is a start to preparing that mind.
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Penny, D. Defining moments. Nature 442, 745–746 (2006). https://doi.org/10.1038/442745a