Where Does the Genetic Code Come From? An Interview with Dr. Charles Carter, Part II

“Translating the genetic code is the nexus connecting pre-biotic chemistry to biology.” — Dr. Charles Carter

Last week we discussed the general question of how the genetic code evolved, and noted that the idea of the code as merely a frozen accident — an almost completely arbitrary key/value pairing of codons and amino acids — is not consistent with the evidence that has been amassed over the past three decades. Instead, there are deeper patterns in the code that go beyond the obvious redundancy of synonymous codons. These patterns give us important clues about the evolutionary steps that led to the genetic code that was present in the last universal common ancestor of all present-day life.

Charles Carter and his colleague Richard Wolfenden at the University of North Carolina Chapel Hill recently authored two papers that suggest the genetic code evolved in two key stages, and that those two stages are reflected in two codes present in the acceptor stem and anti-codon of tRNAs.

In the first part of my interview with Dr. Carter, he reviewed some of previous work in this field. In the present installment, he comments on the important results that came out of his two recent studies with Dr. Wolfenden. But before we continue with the interview, let’s review the main findings of the papers.

The key result is that there is a strong relationship between the nucleotide sequence of tRNAs, specifically in the acceptor stem and the anti-codon, and the physical properties of the amino acids with which those tRNAs are charged. In other words, tRNAs do more than merely code for the identity of amino acids. There is also a relationship between tRNA sequence and the physical role performed by the associated amino acids in folded protein structures. This suggests that, as Dr. Carter summarized it, “Our work shows that the close linkage between the physical properties of amino acids, the genetic code, and protein folding was likely essential from the beginning, long before large, sophisticated molecules arrived on the scene.” Perhaps it also suggests – this is my possibly unfounded speculation – that today’s genetic code was preceded by a more coarse-grained code that specified sets of amino acids according to their physical functions, rather than their specific identity. Continue reading “Where Does the Genetic Code Come From? An Interview with Dr. Charles Carter, Part II”

Where Does the Genetic Code Come From? An Interview with Dr. Charles Carter, Part I.

“I’m more and more inclined to think that we can actually penetrate at least some of the steps by which nature invented the code.” — Charles Carter

The genetic code is one of biology’s few universals*, but rather than being the result of some deep underlying logic, it’s often said to be a “frozen accident” — the outcome of evolutionary chance, something that easily could have turned out another way. This idea, though it’s often repeated, has been challenged for decades. The accumulated evidence shows that the genetic code isn’t as arbitrary as we might naively think. And more importantly, this evidence also offers some tantalizing clues to how the genetic code came to be.

This origins of the genetic code has long been a research focus of University of North Carolina biophysicist Charles Carter, and his UNC enzymologist colleague Richard Wolfenden. They authored a pair of recent papers that suggest behind the genetic code are actually two codes, reflecting key steps in its evolution. Dr. Carter kindly agreed to answer some questions about the papers, which present some interesting results that add to the growing pile of evidence that the genetic code is much less accidental that it may seem.

These papers deal with the machinery that implements the genetic code. Conceptually the code is simple: it is a set of dictionary entries or key-value pairs mapping codons to amino acids. But to make this mapping happen physically, you need, as Francis Crick correctly hypothesized back in 1958, an adapter. That adapter, as most of our readers know, is tRNA, a nucleic acid molecule that is “charged” with an amino acid.

But the existence of tRNAs creates another coding problem: how does the right tRNA get paired with the correct amino acid? The answer to this question is at the heart of the origin of the genetic code, and it’s the subject of these two recent papers. More about this story, as well as the first part of my interview with Dr. Carter, is below the fold. Continue reading “Where Does the Genetic Code Come From? An Interview with Dr. Charles Carter, Part I.”

Science Caturday: One Code, Two Code…

Like a DNA nucleotide, this LOLcat is capable of playing multiple roles. It is good for creation vs. evolution, and so much more. Global warming vs. something else? You are covered. Homeopathy vs. physics? Done. Duons vs. the genetic code? In the bag.

Duons vs. the genetic code? What is a duon?

Good question. A duon is a DNA nucleotide that can do two roles. This perhaps makes it a rather lame nucleotide. DNA nucleotides have a lot of potential tasks they can do (eg, help encode an amino acid, be part of a protein binding site, indicate a splice site, etc) as part of their role storing information in our cells. The idea that a nucleotide might be subject to evolutionary pressure from several different tasks simultaneously is nothing new.

There is, as Emily Willingham points out at Forbes, no real “duon” controversy outside the minds of the folks that wrote the press release (and, perhaps, John Stamatoyannopoulos, if the press release quote is accurate, which I suspect it might be based on his advocacy for the ENCODE Consortium’s “junk DNA is functional” boondoggle). These researchers have provided some evidence to support the hypothesis that evolutionarily conserved codon bias (using one codon, of the several possible for an amino acid, in the genetic code more than expected by chance) is due to selection to maintain transcription factor binding sites.

This is not an unreasonable hypothesis, but it is hardly shocking, hardly requires a new term, and is hardly a controversy.