The Origin of Genetic Heredity

Raquel Nunes Palmeira , Nick Lane, Andrew Pomiankowski

The dominant view that genetic heredity arose in an RNA world stems from the ideas of Francis Crick and Leslie Orgel, who suggested that early nucleotide polymers could act as both phenotype and genotype and that the genetic code was shaped by a frozen accident. At around the same time, Carl Woese proposed a different model: that naturally occurring early translation was biased by weak stereochemical affinities between nucleotides and amino acids, producing what he called statistical proteins. This alternative was never dismissed on empirical grounds but fell out of favour as gene-level selection and the idea of an RNA world became entrenched. This review re-examines these competing models by tracing the origins of their two central divergences: whether selection first acted on naked genes or whole protocells, and whether early coding depended on stereochemical interactions. We summarise how these assumptions arose, how they have shaped theoretical models, and how they constrain explanations for the emergence of translation. Focusing first on the level of selection, we outline why models of naked-gene evolution face inherent obstacles related to information integration, whereas protocell-level models naturally favour the coexistence of sequences. We then turn to the question of stereochemical interactions in early translation. We consider the predictions of each hypothesis for the structure of the genetic code and compare these to the patterns observed today. Finally, we review the experimental evidence for amino acid-nucleotide interactions and outline the key empirical gaps. Together, these lines of evidence clarify which assumptions in classical models remain viable and point to the most informative experiments that can be done to elucidate the origin of heredity.