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Another Remarkable DNA Rescuing Machine

Helicase.jpg

With its double helix structure, DNA is long and its strands can sometimes form complex tangles. The detangling spray you use on your kids' hair won't work on these. One particular “unwinder” is superb at unwinding 4-stranded structures, and it works in everything from bacteria to humans.

The cell nucleus is a beehive of activity. Transcription machines read out portions of DNA for translation into protein; epigenetic machines tag certain genes for expression or repression; hormones bring signals in from the outside. The biggest job of all is faced at each cell division, when every base pair of DNA has to be replicated accurately. That’s 3.2 billion “letters” in a human cell.

Between replications, DNA can tangle into a number of complex structures. Some of these are composed of four strands that form stable structures called G-quadruplexes or G4s, so named because they tend to be rich in guanine. They are not uncommon, but it is not clear if they have a function. One thing is certain: they pose big problems during replication.

Fortunately, there is a machine that can unwind these G4s quickly and efficiently. Called Pif1 helicase, it is conserved from bacteria to humans. When it is absent or damaged, chromosome instability can result -- a catastrophe that can lead to cell death or cancer. Pif1 is also implicated in the silencing of telomerase, the enzyme that adds telomeres, or end caps, to chromosomes. Uncontrolled telomerase is also implicated in cancer. The Pif1 machine has a vital job. (For more background on DNA helicases, see Jonathan M.'s recent coverage here and here.)

A team from American and German universities took a closer look at Pif1. Publishing in Nature, Paeschke et al. found that Pif1 suppresses genome instability by quickly unwinding G-quadruplexes before they can stall the replicating machine, DNA polymerase. In a review of the work in the same issue of Nature, Sergei Mirkin showed a simplified diagram of how it fits in the replication scheme. Because the double-helix DNA strands are separated during replication, the single strands behind the replication fork are prone to G4’s when attractive forces between guanines allow loops to form. Pif1 finds these G4 motifs, binds to them, and unwinds them so that replication can proceed.

The Pif1 helicase machines are very efficient. They worked 100% of the time on test strands from yeast in vitro. Most interesting, the researchers found that when the gene for human Pif1 was inserted into a yeast genome, it worked, too.

There are many helicases in a cell for various functions, but no other one is as fast and effective on G4 motifs as Pif1. Mirkin says,

S. cerevisiae [yeast] has two Pif1-family helicases: Pif1 and Rrm3. Pif1 prevents replication-fork stalling at G-quadruplexes, whereas Rrm3 helps to resolve 'collisions' between transcription and replication processes along DNA. Paeschke et al. demonstrate that Pif1-family helicases from various species unwind G-quadruplexes extremely quickly and efficiently. Many other DNA helicases were shown to unwind G-quadruplexes, but the Pif1 helicases seem to be the best for this task. Moreover, G-quadruplexes are by far these helicases' favourite substrates. (Emphasis added.)

How did this amazing machine come about? They don't say. They simply assume that Darwinian evolution did it somehow. For instance, Mirkin says, “The Pif1 helicase family of enzymes has evolved to disentangle these structures efficiently.” Evolution even evolved all the cell’s DNA machines: “Because formation of unusual DNA structures is a recurrent problem, cells have evolved defensive mechanisms to deal with them.”

Because Pif1 is “highly conserved, from bacteria to humans,” Mirkin applied evolutionary logic (intentional oxymoron) to the question of when it evolved: “Thus, unraveling G-quadruplexes seems to be a conserved function of Pif1 helicases that arose very early in evolution.” It must be an “evolutionarily conserved mechanism” (another oxymoron).

What did the researchers in the original paper say about evolution? Not much. They were really surprised, though, to see human Pif1 work in a yeast cell:

The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast.

This must be the “If-it-works-don’t-fix-it” theory of evolution. The Editor’s Summary of the paper states, “The ability of the human protein to complement in yeast demonstrates the importance of this activity throughout evolution.”

So here we have an extremely important machine in the simplest living cells doing outstanding work, and the authors attribute it to blind, unguided processes.

It is extremely rare in evolutionary papers like this to find authors attempting to describe how a complex molecular machine evolved. What sequence of accidental mutations subject to unguided processes caused it to “arise” in the first place? How does it recognize G-quadruplexes? Once it is able to recognize them, how does it “know” what to do? How does it come to work in an “exceptionally potent” manner, only to stay virtually unchanged for billions of years?

Evolutionists don’t explain these things; they only assume them. The cell needed it, because of “the importance of this activity,” so natural selection to the rescue! It not only “arose,” it “arose very early” -- somehow.

If pushed to account for its origin, an evolutionist might say, “Well, if evolution didn’t invent Pif1, we wouldn’t be here.” That would be the application of a kind of biological “anthropic principle” -- not an explanation, but a post-hoc copout taking for granted that natural selection can accomplish any task given to it. If pushed to ask why it is conserved, they might say, “If it works, don’t fix it.” But why stop there? A bacterium works. Why proceed up to humans? A theory that amounts to “Some things evolve; some don’t” explains nothing.

Pif1 is potent; evolution is impotent. Natural selection is useless for explaining these things. As biochemist Scott Minnich said in the Illustra Media film Unlocking the Mystery of Life (2002), “We can’t explain these systems by natural law. And, if we’re searching for truth, and, they are in fact designed, if we have to be design engineers to understand these them, then I say, What’s the problem? You know, you go where the data leads you.”

Pif1 adds potent support for Minnich’s prediction from a decade ago: “I think design is back on the table.”

Image: E. coli helicase RuvA/Wikipedia.