Chapter Introduction

17: The Genetic Code

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  • 17.1 Deciphering the Genetic Code: tRNA as Adaptor

  • 17.2 The Rules of the Code

  • 17.3 Cracking the Code

  • 17.4 Exceptions Proving the Rules

MOMENT OF DISCOVERY

Steve Benner

The origin of life has long been an interest of mine, particularly the evolution of nucleic acids and the reason that ribose was selected as the sugar used in RNA. In the 1950s, Stanley Miller and others showed that ribose can be produced abiotically (without enzymes), but Miller and others had noted that ribose is not very stable. This is because, in the lab, ribose and other five-carbon sugars are made under alkaline conditions from simple organic precursors, formaldehyde and glycolaldehyde; a high pH encourages reasonable reaction rates, but the ribose product tends to break down quickly into a brown tar.

Although we weren’t actually studying this particular problem, a comment from a colleague about “solving the ribose problem” coincided with a trip I took to Death Valley to collect rocks. While there, I began musing about the borate-containing rock samples I was finding, and thinking about the long-known observation that borate can bind to organic molecules that contain 1,2-dihydroxyl groups—exactly the kind of chemical structure present in ribose.

When I returned to the lab, it only took about a day and a half to show experimentally that ribose could be made stably at high pH in the presence of borate. Because borate is abundant in nature, it seems likely that it stabilized the prebiotic production of ribose, providing a simple and logical explanation for the presence of ribose on the early Earth. It was satisfying to make this discovery, but also humbling to realize that borate-carbohydrate interactions have been known since the 1950s. So the answer to the ribose stability problem has been staring us in the face all along!

—Steve Benner, on discovering that borate minerals stabilize ribose

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The discoveries that DNA is composed of complementary strands and that it holds the instructions for all the proteins in an organism were huge advances in our understanding of the flow of biological information. However, proteins and nucleic acids are very different types of chemicals, and after the structure of DNA was solved, how the sequence in a chain of nucleotides determines the sequence of amino acids in a protein was not immediately apparent. The next 10 years brought several discoveries that revealed the fascinating processes by which DNA is decoded to produce proteins.

The linear nucleotide sequence of mRNA is translated into protein by tRNA molecules that carry amino acids and contain nucleotide sequences (called anticodons) that pair with complementary sequences (codons) in the mRNA. Different amino acid–carrying tRNAs are lined up according to the mRNA sequence, and the amino acids are stitched together by the ribosome, resulting in a polypeptide with a linear order of amino acids that corresponds to the linear order of codon sequences in the mRNA. The discovery of the translation process and the genetic code, the matching of each codon to the amino acid it specifies, is a fascinating story and a landmark in modern science.

Amino acids and nucleotide bases have no obvious chemical relationship, and therefore it is not at all obvious how given amino acids became matched to particular trinucleotide sequences. Yet all organisms—bacteria, yeast, amphibians, plants, archaea, and humans—use the same genetic code, with only a few minor modifications. Presumably, once the code had evolved, it resisted change. The universality of the genetic code provides amazingly strong, molecular evidence for evolution, much more compelling than arguments based on body shapes and the fossil record.

This chapter presents an overview of the genetic code and how it works. We first look at how the tRNA molecule functions in decoding, and how it is exquisitely designed to take advantage of the “degeneracy” of codons, enabling one tRNA to decipher more than one codon. We also examine how the genetic code can resist the harmful effects of single-nucleotide mutations. These special features indicate that the genetic code is not simply an accident of evolution, but has been fine-tuned by natural selection. The last universal common ancestor (LUCA) must have existed for sufficient time to hone the code prior to divergence of the different domains of life as we know them today. Finally, we look at exceptions to the genetic code—variations that only reinforce the idea that all life forms evolved from LUCA and its genetic code. How the genetic code came into being during evolution is still a perplexing problem. We examine this issue, too, even though there are no clear answers.