Science Literature

Robert Deyes

Switches, rheostats, electrical circuits and complex feedback loops that regulate household devices as well as national power grids are things that we have become so accustomed to in our own lives that we generally take them for granted. That is, until they break down. We saw this on a massive scale in the summer of 2003 when New York and other US and Canadian cities were brought to a stand still as power blackouts swept the east coast. A New Scientist report at the time claimed a total of 50 million people were affected (Ref 1). Needless to say, it took several days to bring things back to normal. The economic impact of the catastrophe cost the American and Canadian governments billions of dollars (Ref 1).

Switches turn genes on and off in the cell

Incredibly, regulated circuits and switches also exist inside the microscopic world turning genes on at the precise moments that their products are required and shutting them off when those same products become unnecessary, superfluous or even detrimental. In a fascinating study headed by a group at the Wistar Institute in Philadelphia it has now become clear that histones - proteins that are involved in packing DNA into individual chromosomes - play a fundamental role in regulating which genes are turned on and off in the cell (Ref 2). It appears that small molecular groups attached onto these histone proteins can serve as on/off switches that modulate which genes are on or off at any given moment. These molecular groups become attached to the histones as a result of multi-component machines that turn on genes. Karl Henry's group at the Wistar has revealed the functionality of one of these multi-component machines called the SAGA complex that attaches a molecular group called ubiquitin onto one of the Histones (Ref 2). What is surprising about the SAGA complex is that the removal of the ubiquitin molecular group from the Histones does not turn genes off. Rather it seems that both the addition and subsequent removal of ubiquitin, both by the SAGA complex, provide an essential sequence for turning genes on (Ref 2). This finding places an extra level of complexity to the previously held view that genes could be turned on or off through simple on/off switches. Now it appears that such switches operate through a specified order of molecular changes. In the case of SAGA, the correct order is absolutely critical if genes are going to be turned on correctly.

So it is that we learn that the 'conversion' of the genetic instruction into protein through the initial step of transcription involves more than polymerases - the reading molecules that chug along the DNA and generate RNA. It is a carefully planned, well-orchestrated series of events involving molecular switches. We see a complexity that intuitively does not seem to be accessible to unguided assembly. As mathematician David Berlinski quipped, "wherever the biologist looks, there is complexity beyond complexity, the entanglement of things ramifying downward from the organism to the cell" (Ref 3).

What caused the east coast electricity blackout? According to the New Scientist report there were two crucial pieces of software that failed on that frightful day (Ref 1). As alarm systems failed, more lines shut down and voltages fluctuated, the entire network spun out of control with the inevitable consequence of a massive power shut down. America suffered its worst power cut in recent memory because the correct order of processes and procedures so essential for the smooth running of an electricity grid had not been met. What happened on that horrific day during the heat of the summer sun was due to operator failure and could have been easily prevented. The New Scientist report mentions, for example, that one engineer left for lunch when a critical maneuver needed to be carried out (Ref 2). It is profoundly ironic that one of America's worst power failures should occur at precisely the moment that intelligent agency left the scene. As with man-made designs, evidence points to an intelligence behind the precision functioning of the cellular world.

References

1. Celeste Biever (2003) 'Preventable' failures caused US power blackout, New Scientist, 20th November, 2003

2. Karl W. Henry, Anastasia Wyce, Wan-Sheng Lo, Laura J. Duggan, N.C.Tolga Emre, Cheng-Fu Kao, Lorraine Pillus, Ali Shilatifard, Mary Ann Osley, Shelley L. Berger (2003) Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation mediated by SAGA-associated Ubp8, Genes & Development Vol 17 pp2648-2663

3. David Berlinski (1996), The Deniable Darwin, http://www.discovery.org (see 'Articles by Center Fellows')