PROOFREADING AND
DECEPTION?
By Mike Gene (
Several years ago, I used the hypothesis of design to predict the process of transcription would be proofread [1]. The example was used simply to refute the commonly held notion of the concept of Intelligent Design as one that cannot generate testable hypotheses. Since this time, I have encountered reactions among a few critics (in cyberspace) attempting to cast doubt on the sincerity of this prediction. Put bluntly, some skeptics have accused me of deception, where I was supposedly aware of transcriptional proofreading, yet pretended to be ignorant in order to create the illusion of a validated prediction. This accusation, however, leads me to suspect my original prediction was more significant than originally thought. If my teleological prediction was truly irrelevant or weak, it is difficult to understand why people would go to the extreme of invoking a deceptive ploy on my part. The accusation of deception represents an attempt to discredit the prediction. But one would be motivated to discredit the prediction only if it was deemed significant.
There are two basic stories about my supposed deception.
Story #1: It is claimed that transcriptional proofreading is a well-known phenomena in molecular biology and has been so for some time. As I mentioned in my original essay, I was unaware of any proofreading ability for RNA polymerase at the time I came up with the prediction. Since transcriptional proofreading was a well-known phenomena, I was thus either ignorant of basic molecular biology or being deceptive.
Story #2: As I noted, the prediction stemmed from pondering the fact that both translation and DNA replication were proofread, in that I had just finished a short essay on translational proofreading for an e-mail listing that I was on. According to this story, I was doing a PubMed search on “translational proofreading,” and the Jeon and Agarwal paper I originally cited as validation appeared during this search. Thus, supposedly I “post-dicted” something I had found while searching for things related to translation.
Let me dispose of these stories.
Story #1 Refuted
I originally came up with my prediction (and posted it to the internet) in 1999. At this time, transcriptional proofreading was not common knowledge in molecular biology. One way to verify this is to check the 2004 edition of Lodish et al.’s Molecular Biology of the Cell. It is not discussed. And neither is it discussed in Lewin’s 2000 edition of Genes.
Or, we could look to the review literature. When a topic matures to a point where it has acquired sufficient data and theory, a review paper is often submitted to a journal. As of 2004, I have not been able to find one paper that reviews the topic of proofreading during transcription.
Molecular biology is a large field of inquiry that grows exponentially. I wouldn’t classify transcriptional proofreading as a basic and well-known concept in molecular biology (at least in 1999). Proof-reading during DNA replication? Sure. But transcription? Nah. Doubt me?
Consider the lecture notes from a Genetics course [2]:
Unlike DNA replication, RNA transcription involves no proofreading.
(Why?)
This claim represents common thought in molecular biology. In fact, the question “why?” seems to have an intuitive answer (at least, from the perspective of Darwinian evolution). Another Genetics course [3], drawing from Tamarin, R. 1996. Principles of Genetics, 5th ed., provides the answer:
P. 267, #2 Given that RNA
polymerase does not proofread, do you expect high or low levels of error in
transcription as compared with DNA replication? Why is it more important for
DNA polymerase to proofread compared with RNA polymerase?
You would expect high levels of error in
transcription as compared to DNA replication. Proofreading is important in DNA
replication because mistakes in DNA replication will be passed to offspring
(either as daughter cells or through gametes) as mutations. However, RNA's are
short lived in the cytoplasm and thus mistakes are not permanent. It is better
to not proofread and thus speed up transcription.
This is a theme picked up by other biologists:
RNA polymerase does not proofread (not necessary because multiple transcripts are produced from a single gene) [4]
And from another course’s PowerPoint slide [5]:
RNA polymerase does not proofread
Makes many copies of RNA from DNA
Errors not as critical in RNA as in DNA
The simple fact is that “common knowledge” in molecular biology was the RNA polymerase/transcription did not involve proofreading:
RNA polymerase does not proofread as RNA is synthesized. [6]
RNA polymerase does NOT proofread the mRNA [7]
RNA polymerases have no proofreading
activity (error rate 10-4). [8]
What’s one difference between DNA replication and transcription? [9]
Compared to DNA synthesis (replication), RNA synthesis (transcription)
has:
->no proofreading
Thus, Story #1 is refuted by the simple fact that transcriptional proofreading was not common knowledge in molecular biology. My ignorance of the process was shared by many.
Story #2 Dismissed
Story #2 has me scanning through PubMed, looking for articles to incorporate into my essay on translational proofreading, only to stumble upon transcriptional proofreading articles. This story is easy to dismiss. A PubMed search with “translational proofreading” does not retrieve the Jeon and Agarwal paper cited in my original essay outlining the prediction. Secondly, and more importantly, no PubMed search was conducted to write my comments about translational proofreading. That short essay was written after reading through some articles in Science, the most widely-read scientific journal. The reading of these articles lead to the writing of the short essay [10] and this thinking led me to formulate the prediction about a month later. There is no need to invoke any secret PubMed searches as part of my “research” to write the essay on translation, for there was no “research.” I was simply reading articles from vol. 285 of Science. That I encountered these articles in Science is about as remarkable as someone encountering a story in the NY Times.
The Significant Point
What matters is that this simple example of a verified prediction (from my perspective of original ignorance) refutes the commonly held belief that ID Thinking can not lead to testable hypothesis that shed light on the biotic world. And even if hardcore skeptics cling to the notion that the prediction was rooted in deception, that would not matter. The strength of a prediction does not come from its ability to foretell the future. It comes from the insight provided by the logic of the hypothesis. And in this case, the hypothesis of Life’s design allowed me to accurately infer something about the biological world.
At this point, the skeptic will be quick to point out that transcriptional proofreading can also be accounted for by Darwinian evolution. But there is a problem with this response. Darwinian evolution also appeared to do a good job of accounting for the lack of proofreading during transcription. That is, Darwinian evolution nicely explained a reality that did not exist.
Recall the common explanation for RNA polymerases presumed lack of proofreading activity:
You would expect high levels of error in
transcription as compared to DNA replication. Proofreading is important in DNA
replication because mistakes in DNA replication will be passed to offspring
(either as daughter cells or through gametes) as mutations. However, RNA's are
short lived in the cytoplasm and thus mistakes are not permanent. It is better
to not proofread and thus speed up transcription.
This is essentially an appeal to the Blind Watchmaker. That is, errors that would be passed to offspring are important, not transient mistakes divorced from replication. In other words, the Blind Watchmaker cares only that things “work” and what “works” is judged only in reproductive terms. In this case, it would just be better to accelerate transcription rates rather than worry about the transient mistakes that are not heritable.
Nothing in Darwinian theory led anyone to suspect that RNA polymerase was proofreading. In contrast, I have illustrated ID thinking did indeed lead me to suspect this.