Ned Seeman’s legacy

‘How Darwin’s “struggle for life” happens has been largely unexplored at the molecular level’, wrote Edith Heard, director-general of the European Molecular Biology Laboratory, recently. She was talking about developing a better molecular-scale picture of organisms in their natural environments rather than of bits of them in the lab. But another way to read her comment is that the fundamental processes of Darwinian evolution – replication, mutation, and selection – are not much explored at the level of single molecules.

Of course, in organisms the effects of genetic mutations become visible to selective pressure only at the level of the phenotype. There is a world of complexity separating inherited genotypic mutations from the consequences they have for fitness. But the connection is much more direct in viruses, with consequences of which SARS-CoV-2 is making us painfully aware. And the widespread belief is that Darwinian natural selection began among even simpler molecular entities – perhaps even single molecules, as posited in the RNA world hypothesis for the origin of life.

Templated replication and exponential growth of single DNA-like strands was first demonstrated several decades ago and has also been observed in RNA enzymes that can display competition between variants. Such a process only becomes Darwinian if there is both mutation and selective pressure that discriminates between mutants. Both of those features have now been demonstrated in synthetic DNA constructs, producing a prototype molecular system that should offer a simple and tunable minimal model of ‘how Darwin’s “struggle for life” happens.’