Chemical Origins of the Genetic Code: Lost in Translation

MRC Laboratory of Molecular Biology
Protein and Nucleic Acid Chemistry

The coded biosynthesis of proteins – the translation of genetic information into function – is a defining pillar of molecular biology, and a prerequisite for life.

In no small part due to prodigious research undertaken at the LMB itself, the mechanism of translation in extant biology – life in its current form – is known in exquisite atomistic detail, unimaginable to the pioneers of nascent molecular biology. We know how it works, where it happens, and how to manipulate it. We know the underlying genetic code that governs translation, and we know that curiously formed complexes of RNA – tRNAs – are responsible for delivering the right amino acid, at the right time, during protein biosynthesis. Yet the picture is incomplete, and fundamental pieces are missing. One profound dichotomy is that extant translation depends vitally on an ensemble of proteins, yet these very proteins could not have emerged before a means to generate them. The genetic code is essentially universal amongst cellular life forms, and yet myriad alternative codes could feasibly perform the same role. How did our genetic code emerge, why should it be the way it is, and how did specific sequences of nucleotides (codons) get assigned to specific amino acids, before “biology” even existed?

In collaboration with a multidisciplinary team in the Sutherland group, I seek to tackle these questions by studying truncated mimics of extant tRNAs from the perspective of a mechanistic chemist - how they might acquire - and lose - certain amino acids selectively, and how amino acids might be transferred efficiently from one tRNA to another, all without the aid of the colossal biomolecular machinery that underpins life as we know it.