Monday, June 12, 2006

A Genetic Switch

An article published by the Howard Hughes Medical Institute entitled "Genetic Switch for Maturation Discovered," which can be accessed at the indicated web address, provides some food for thought. A snippet from the article appears here. My interspersed comments are clearly identified.

"The genetic maturation switch identified by the researchers, called DHR4 , is a member of a family of genes that encode proteins called nuclear receptors. These receptors, triggered by hormones, each control a large number of other genes, giving them a critical role in coordinating complex body processes."

[Bradford]: It is precisely such genes that should be the focus of attention by evolutionists and advocates of intelligent design. If the existence of eukaryotic organisms results, to a great degree, from a process dependent on selected random mutations then evidence for a capacity to generate novel complexes of genes triggered by hormones is essential. The potential of such gene complexes to evolve offers IDers opportunities to make predictions. As engineers or others who design products are aware, a seemingly simple modification of one part can entail the necessity to modify other interacting parts as well. Any attempt to describe the potential of genetic change required to generate a contemplated morphological feature needs to incorporate an estimate of inhibiting factors represented by existing genomic properties. Quantification is difficult due to an enormous number of variables, incomplete knowledge and an inherent uncertainty pertaining to data associated with natural history. Nevertheless an honest search for truth demands that theory encompass these kinds of details with the outcome not presumed.

"Thummel and his colleagues began studying DHR4 because of its pattern of activity in the developing fly and other insects. “Virtually nothing was known about DHR4 , but we found it intriguing because it is expressed transiently during the very early stage of metamorphosis,‿ he said. DHR4 was also intriguing to the scientists because the gene produces a so-called “orphan‿ nuclear receptor, whose activating hormone was unknown.

To discern the function of DHR4 , the researchers knocked out the gene in two different ways. Co-author Charles created a mutant form of the fly that completely lacked a functioning gene. And Thummel and his colleagues used a technique called RNA interference that allowed them to selectively inactivate the DHR4 gene at different stages of the fly's growth."

[Bradford]: Gene knock out is an effective tool. It has been mentioned as one that might be used in connection with experiments testing the capacity of a biological function to evolve under selective pressure. Rapidly reproducing organisms would be used and the time frames could span years.

"By analyzing the effects of these two types of gene inactivation, the researchers teased apart two distinct roles of DHR4 in maturation. They found that one effect of DHR4 loss was that larvae of the mutant flies stopped eating too early in development, initiating behaviors that led to early pupa formation. These pupae developed into smaller, lighter adult flies. “These mutants eat and grow normally until their last larval stage,‿ said Thummel, “when they stop eating prematurely and go into metamorphosis earlier than they should.‿

The researchers also found that DHR4 -deficient flies showed defects in the process of metamorphosis itself. These defects involved the developmental “circuitry‿ controlled by the key insect steroid hormone ecdysone, known to be a major orchestrator of biological processes throughout a fly's development and a critical regulator of metamorphosis.

“The discovery of DHR4 's role in repressing the genetic cascade triggered by ecdysone was very gratifying, because it filled in a piece of an important puzzle,‿ said Thummel. “In flies, the work of many laboratories has produced an elegant, detailed model of the developmental machinery triggered by ecdysone. However, there has been one piece missing, which we have been seeking for many years - how the earliest response to ecdysone is repressed.

“These genes switch on and off really fast,‿ explained Thummel. “We knew that ecdysone turns them on, but we never knew what turned them off. Now we know that DHR4 is one of the critical components required for shutting down that response, so proper development can proceed."

[Bradford]: This brings to mind comments of Phil Skell, a retired professor with a PhD in chemistry. Dr. Skell has argued, based on his interviews of researchers, that theories of natural history, including evolution, are irrelevant to modern research and scientific progress. I would concur.


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