Re: Trevors and Abel paper

From: Pim van Meurs <>
Date: Sun Oct 02 2005 - 17:39:26 EDT

Just for "fun" I decided to research some of the claims in the paper

<quote author="Trevors et al">Similarly, it is difficult to envision how
the laws of physics and chemistry could explain encryption/decryption.
No physicochemical link exists between programmed nucleotide sequence
and amino acid functional sequence.</quote>

As I have already shown, the argument is fallacious since it ignores the
stereochemical origin of the code proposed by Woese.

So let me quote from a recent paper which presents a good overview of
the literature

RNA Affinity for Molecular L-Histidine; Genetic Code Origins
Irene Majerfeld, Deepa Puthenvedu, Michael Yarus
J Mol Evol (2005) 61:226–235 DOI: 10.1007/s00239-004-0360-9

<quote author="Majerfeld et al">
The 20 standard biological amino acids are interesting ligands for RNA.
They present chemically varied surfaces, and RNAs response to these
chemical challenges should be relevant to the intrinsic possibilities of
RNA–peptide interfaces. Furthermore, stereochemical theories of the
origins of the genetic code (Woese et al. 1996) propose that
chemical\affinities between codons and/or anticodons and amino acids
determined at least some codon assignments.
Such affinities between RNA and amino acids are known to be real and
varied. The first was found in the group I self-splicing RNA, where
arginine acts as a competitive inhibitor for the guanosine splicing
co-factor. Binding is therefore within the active site (Yarus 1988).
Because this binding site depends on conserved arginine codons (Yarus
and Christian 1989), the group I active center appears to be a
‘‘molecular fossil’’ of codon assignment to arginine (Yarus et al.
2005), possibly dating from the RNA world.The example of the group I
active center also
suggested that triplet–amino acid chemical association might be best
observed within longer, more stable oligonucleotide foldings.
If these findings generalize, similar associations between coding
sequences and amino acids might be recaptured within the amino acid
binding motifs of newly selected RNA aptamers isolated using
selection–amplification or
A number of such aptamers have been isolated and their binding sites
identified by conservation, NMR, and/or chemical probing. These include
an aptamer for tryptophan-agarose (**Famulok and Szostak 1992**),
several aptamers for arginine (**Burgstaller et al. 1995**; **Connell et
al. 1993**; **Connell and Yarus 1994**; **Famulok 1994**; **Geiger et
al. 1996**; **Yang et al. 1996**), valine (**Majerfeld and Yarus
1994**), isoleucine (**Majerfeld and Yarus 1998**), tyrosine
(**Mannironi et al. 2000**), phenylalanine (**Illangasekare and Yarus
2002**), glutamine (**Tocchini-Valentini**, personal communication;
**Yarus et al. 2005**), and leucine (**Majerfeld and Yarus, unpublished;
**Yarus et al. 2005**), as well as histidine and tryptophan (this work;
Yarus et al. 2005).

I indicated with ** the references in this paper not mentioned in the
Trevors and Abel paper. They quote a Yarus 2000 paper as part of a long
selection of papers which they reject as

<quote authors="Trevors et al">All code origin models have problems and
lack detail. In addition, no physical mechanism has been suggested for
the source of abstract genetic instructions themselves. New formats and
approaches are needed to investigate the origin of instructions, coding,
biochemical pathways, cycles, metabolism, and life itself.>/quote>

Which is contradicted even in Yarus 2000 paper Yarus, 2000 M. Yarus,
RNA-ligand chemistry: a testable source for the genetic code, RNA 6
(2000), pp. 475–484 which describes the finding for arganine

<quote author="Yarus 2000">In the genetic code, triplet codons and amino
acids can be shown to be related by chemical principles. Such chemical
regularities could be created either during the code's origin or during
later evolution. One such chemical principle can now be shown
experimentally. Natural or particularly selected RNA binding sites for
at least three disparate amino acids (arginine, isoleucine, and
tyrosine) are enriched in codons for the cognate amino acid. Currently,
in 517 total nucleotides, binding sites contain 2.4-fold more codon
sequences than surrounding nucleotides. The aggregate probability of
this enrichment is 10[minus sign]7 to 10[minus sign]8, had codons and
binding site sequences been independent. Thus, at least some primordial
coding assignments appear to have exploited triplets from amino acid
binding sites as codons.</quote>

And supported by many findings so far.

<quote author="Majerfeld et al">
If there is association between triplets and their cognate amino acids,
coding sequences will appear in binding sites
more frequently than chance suggests. Statistical analysis (Knight and
Landweber 1998; Yarus et al. 2005) compares the abundance of coding
triples within the aptamer binding site to their abundance in the
nonsite sequences from the same molecule. Data exists for eight amino
acids, and significant associations were found for both codons and
anticodons, In fact, the overall probability of the null hypothesis
—that there is no association between these eight kinds of amino acid
binding sites and cognate coding triplets—now stands at 5.4 10^-11. This
is exceedingly unfavorable to the null hypothesis and in support of
robust relationship between coding triplets and amino acid affinity,
especially given that the data include both strongly negative and
positive cases.</quote>

In light of these findings, many of which were already available to
Trevors and Abel, I find their statements quite puzzling.

So far the paper is flawed in the following concepts

1. No link between "physical mechanism has been suggested for the source
of abstract genetic instructions themselves". When in fact they quote at
least one such paper and seem to be unfamiliar with the many other
supporting papers, extending the findings beyond the single arganine
example in Yarus 2000 whose paper presents a 'testable source for the
genetic code'
2. The confusion of information content in the genome not being able to
be generated by chance and regularity. Also a common ID claim which on
closer scrutiny is not only disproven by simple experiments but also
theoretically flawed.

And that's just after quickly browsing its claims.

An "interesting" paper though in that it mirrors many of the ID claims
often in slightly different language. One would almost conclude that
much of the claims were guided by ID arguments. Irregardless, their
claims fail not just because of the presence of testable regularity and
chance pathways but also because of the flawed theoretical foundations
of these ID (like) arguments.

Did I miss anything in the Trevors and Abel paper where they address why
they reject the link between stereochemistry and the code? They do not
use the term, they do reference at least one relevant paper but reject
it as insufficient but fail to mention the followup evidence.
Similarly they reference Knight 1999 but do not mention Knight 1998

Trevors and Abel quote:
Knight et al., 1999 R.D. Knight, S.J. Freeland and L.F. Landweber,
Selection, history and chemistry: the three faces of the genetic code,
Trends Biochem Sci 24 (1999), pp. 241–247.

But not:
Knight RD, Landweber LF (1998) Rhyme or reason: RNAarginine interactions
and the genetic code. Chem Biol 5 :R215–220

I already mentioned ORIGINS OF THE GENETIC CODE: The Escaped Triplet
Theory by Michael Yarus, ­J. Gregory Caporaso, and ­Rob Knight in Annual
Review of Biochemistr Vol. 74: 179-198

There is very significant evidence that cognate codons and/or anticodons
are unexpectedly frequent in RNA-binding sites for seven of eight
biological amino acids that have been tested. This suggests that a
substantial fraction of the genetic code has a stereochemical basis, the
triplets having escaped from their original function in amino
acid-binding sites to become modern codons and anticodons. We explicitly
show that this stereochemical basis is consistent with subsequent
optimization of the code to minimize the effect of coding mistakes on
protein structure. These data also strengthen the argument for invention
of the genetic code in an RNA world and for the RNA world itself.

 From the paper

Stereochemical Origin
The Three Hypotheses Could All Be Correct

The authors discuss the common three scenarios/hypotheses and shown how
all three may have played a role in the evolution of the genetic code.

Stereochemical Origin
We argue that the stereochemical hypothesis (3) is supported by the most
extensive evidence. It states that there is specific affinity between
codons or anticodons and amino acids. The stereochemical hypothesis is
an idea with an intrinsic experimental program because it predicts that
the genetic code relies on interactions that should be observable in a
modern laboratory. We have tested the idea that the coding triplets
arise as essential parts of RNA-like amino acid–binding sites. These
ancestral triplets then escape from amino acid–binding sites to acquire
new functions as codons and anticodons in a more modern translation
apparatus. It is not required that all associations in the coding table
have this character (4), and in particular, we know that the code can
change (see below). The original coding assignments might thus have been
overwritten, using other logic, during later code
evolution. Nevertheless, it seems that many chemical attractions,
manifested as binding affinities, still are reflected in the modern
coding table.

The paper is well worth reading due to its in depth overview of the
hypotheses and their evidences.

In summary, current evidence, construed in a way that minimizes its
significance, supports significantly elevated codon concentration in the
binding sites for isoleucine, and arginine as well as elevated anticodon
concentration for six of the eight amino acids, with the exceptions of
glutamine and arginine. It is intriguing that the one exception to
stereochemical origin is glutamine, an amino acid for which the evidence
of coevolution (see above) is among the strongest. The overall
probability that codons and anticodons for eight amino acids are
independent of their selected cognate binding sites (counting favorable
and unfavorable cases together) is exceedingly low, 5.4 × 10−11.</quote>

So for the only known exception so far, there is significant evidence
for co-evolution.
Received on Sun Oct 2 17:42:39 2005

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