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Thursday, March 01, 2007

A State of Extreme Cognitive Dissonance

Poor old GilDodgen. He's really suffering over his inability to understand some basic biochemistry [Yet Another Irreducible Complexity No-Brainer — Twisted Ropes]. Naturally, he interprets his ignorance to be proof that Intelligent Design Creationism has the answers.

Watch this video to see why GilDodgen is in a state of extreme cognitive dissonance.

Here's what GilDodgen says after watching the video ...
I find the phenomenon of the DNA supercoiling problem and its biochemical solution even more compelling than examples like protein synthesis and the bacterial flagellum, since twisted ropes are familiar to everyone. This might make for another highly persuasive ID mascot.
You are right to start looking around for another mascot since protein synthesis and the bacterial flagellum aren't working for you. But you better be careful about adopting a new poster girl. Maybe you should learn some basic biochemistry before you end up looking even more stupid than usual. Reading a textbook would help.
How could random variation and natural selection come up with a pair of biochemical scissors and a repair mechanism that cuts and splices the twisted DNA molecule in order to relieve torsional tension? What would be the functional, naturally-selectable intermediate steps in a hypothetical stochastically generated evolutionary process? It is clear that there could not possibly be any.
Here's a picture of E. coli topoisomerase I bound to DNA. The mechanism of action of this enzyme is well known. There are four basic steps.

In step I, the enzyme binds to a single-stranded bubble region of DNA. Such regions are characteristic of supercoiled DNA. The enzyme then cuts the DNA in an endonuclease reaction that's often referred to as a "nickase" activity. There are dozens of endonucleases that can carry out this reaction. They are required for DNA replication, repair, and recombination and they evolved for that purpose. Topoisomerases evolved from such nickases.

In step 2, one end of the cleaved DNA is covalently attached to the enzyme via a phosphotyrosince bond. This is likely to be the single evolutionary invention of topoisomerases, although there are other enzymes that have covalently attached nucleic acids. The covalent attachment means that the enzyme remains firmly bound to the site of the nick where it will catalyze a resealing reaction.

In step 3, the other stand of DNA passes through the site of the nicked strand. This is a simple consequence of the fact that the enzyme is holding on to the ends of the cleaved strand.

In step 4, the enzyme catalyzes rejoining of the two ends. This is a ligase reaction. There are dozens of known ligases. They are required for DNA replication, repair, and recombination and they evolved independently to faciliate those reactions. Topoisomerases combine the activities of an endonuclease and a ligase in a single protein but these activities arose originally as separate enzymes. (This was probably a gene fusion event—there are dozens of examples of gene fusions where seprate enzyme activities are brought together in a single protein.)

So the evolution of topoisomerases goes like this. In the beginning, separate nicking enzymes and ligase enzymes were all that was required to relieve tension in front of a replication fork. Over time these two activities became combined in a single enzyme that could quickly bind to DNA under tension, nick one strand, allow free rotation around the other strand, and reseal the nick.

The advantage of having a single enzyme do what used to require two separate enzymes is that the nicking-resealing steps could be faster and this allowed for faster DNA replication. That's probably why there was selection for an enzyme with both activites that didn't let go of DNA.

The last step in the evolution of topoisomerases was selection for the covalent attachment of DNA to the enzyme. This allowed for the possibility of topoisomerase binding to regions that were not under torsional stress in order to relieve supercoils. This, in turn, paved the way for the evolution of much longer DNA strands and circular forms of DNA that could store supercoils. Since supercoiling is related to packaging DNA, this also contributed to the evolution of larger genomes.
I’m suffering from a state of extreme cognitive dissonance. How can educated, intelligent scientists continue to defend the obviously indefensible, in light of what is now known about the nature of living systems (at all levels, not just the biochemical)?
I don't have much trouble coming up with a defense of the "indefensible." But then I have a huge advantage over GilDodgen because I'm a scientist and, as he says, scientists are intelligent and educated.


  1. Great breakdown of the evolution of topoisomerase I.
    I know the mechanism, just didn't know about the evolution of the complex. Good read, and very well defended ;)

    Oh, and that smiley at the end is just the cherry on top of the cake! haha!

  2. Way to go Man - keep hammering on those IDers!

  3. Mr. GilDodgen should stick to posting more of his famous Idiot irony . He's much better at it than he is at science.

  4. You certainly relaxed that problem well. Poor Gil, he is consistently worse than the rest of them. Imagine that!