Archive: Molecular Rheostats Control Expression of Genes

This entry from 21 years ago illustrates the tension between evident design and evolutionary assumptions.

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Molecular Rheostats Control Expression of Genes   01/10/2003
It’s not just the console; it’s the operators, say scientists, that deserve the award for technical excellence. In a Review article in the Jan. 10 issue of Cell, Richard Freiman of Howard Hughes Medical Institute and Robert Tijian of UC Berkeley use adjectives not normally found in dry scientific literature: elaborate, intricate, exquisite, and dramatic. They’re talking not about genes, but the systems that regulate them. A few examples (emphasis added):

• The temporal and spatial control of gene expression is one of the most fundamental processes in biology, and we now realize that it encompasses many layers of complexity and intricate mechanisms.
• … researchers have identified and partly characterized the elaborate molecular apparatus responsible for executing the control of gene expression.
• The molecular machinery responsible for controlling transcription by RNA polymerase II (RNA pol II) is considerably more complex than anyone had anticipated.
• Moreover, working out how subtle changes of the transcriptional machinery can vastly alter activation and repression in the context of the large battery of transcriptional initiation factors will be critical to understanding how elaborate gene expression patterns in metazoan organisms are orchestrated.
• The finding that posttranslational modification of Met4 by ubiquitin controls selective activation of one set of Met4-responsive genes and not another is remarkable and suggests that cells have evolved [sic] elaborate mechanisms to coordinately control gene expression but, at the same time, discriminate between different pathways by subtle mechanisms we have only begun to appreciate.
• It is not hard to envision that these lysine residues therefore serve as critical molecular switches that can respond to different signals in highly specific ways.  In addition, since most proteins contain many lysine residues, transcription factors may undergo multiple modifications simultaneously or in sequential order, pointing to the possibility of generating complex networks of regulatory events.

• Clearly, transcription is exquisitely regulated in all organisms … Future studies in diverse organisms and specialized regulatory pathways should further illuminate how transcription factor modification contributes to the elaborate mechanisms of gene regulation.

Freiman and Tijian note that gene number cannot be the sole determiner of the difference in outward body types between species, such as between a worm (19K) and a human (30K). There’s much more going on. They estimate 10% of the genome is devoted to regulating the expression of genes, and that is largely responsible for the difference between you and the earthworm in your backyard:

In other words, the dramatic phenotypic differences between a worm and a mammal can at least partially be rationalized by differences in the complexity of the regulatory code and not merely gene content. … Regulation by modification not only enhances the functional potential of each individual transcription factor but also provides an effective means of greatly amplifying the functional plasticity of the transcriptional machinery required for combinatorial diversity. This quantum increase in the repertoire of regulatory events ultimately provides the rich tapestry of molecular interactions necessary to direct the diverse arrays of gene expression programs that define complex organisms.

The transcription factors they describe in this paper (ubiquitination, sumoylation, acetylation and methylation) are in addition to the recently-recognized “histone code” system (see our November 4 headline about this), and may be even more vital (emphasis added):

While multiple covalent modifications of histone tails have been well characterized and shown to play a global role in gene expression … we postulate that modification of nonhistone regulatory proteins (i.e., transcription factors) will play an equally important and perhaps more specific role in directly modulating transcription.

One particularly interesting aspect of their paper is that these regulatory programs, by working synergistically or antagonistically, can provide precision control comparable to a skilled audio technician’s hand on a mixing board: “We propose that potential cascades of modifications serve as molecular rheostats that fine-tune the control of transcription in diverse organisms.” So the regulation of gene expression, not merely gene number or content, may be the main factor that produces a navigating lobster, an archery-champion fish, a sonar-operating bat, or a catapulting horse.

Wow! So how did all this complexity evolve? They don’t say, other than to assume it did, couching their just-so story in scientific gobbledygook like:

For example, the transcription factor TFIID is largely conserved [i.e., unevolved] from yeast to humans; however, the diverse programs [intelligent design lingo] of gene expression regulated by this multiprotein coactivator complex [more intelligent design lingo] in unicellular and multicellular organisms have diverged [i.e., they contain differences, but the word assumes evolution] substantially.  Therefore, it is possible [here comes the just-so story] that covalent modification of transcription factors [gobbledygook] , like TFIID, may [imagination] occur in a species-specific manner [no examples or transitional forms provided] , thereby allowing these factors to evolve [with purpose or intent? Illegal procedure] specialized functions [intelligent design lingo] related to their evolutionary [assumption; should be ecological] niche.
(Emphasis and bracketed critique added).

Sorry, but “may” doesn’t cut it in science. Show us how Microsoft Windows evolved into Linux or MacOS X by slow, successive, slight, chance modifications, or else you have no case. To follow that comparison, MacOS X is a lot like Unix, and the different intelligent (more or less) designers behind these diverse operating systems borrow each other’s technology heavily – even incorporating whole subsystems that are “largely conserved.” That does not mean one evolved into the other by purposeless, undirected forces of selection. On the contrary, every piece is integrated to the whole by design, with serious consequences (bugs) when the design specs are not followed. Similarly, in living things, slight modifications often lead to disease and death.
Two running themes in Creation-Evolution Headlines are: (1) the more detail in a scientific paper, the less talk about evolution, and (2) evolution is always assumed, never demonstrated. This paper enters the growing list of examples.
When the secrets of DNA were being uncovered in the 1950s and 60s, people were flabbergasted by processes that were “considerably more complex than anyone had anticipated.” Now that we see that DNA is just a small player in a much bigger field of coordinated activity, like a library in a city, what are we to think? Can Darwinism stand up to these increasing revelations of intelligent design at the fundamental unit of life?