The Implications of Multiple Circadian Clock Origins:
In the Beginning...
Genetics has had an awesome impact on our understanding of basic processes like circadian rhythms, which were mysterious before the incredibly successful marriage between genetics and recombinant DNA technology about 30 years ago. Subsequent to the pioneering work of Konopka and Benzer [1], genetic screens and DNA sequencing in multiple systems (including but not limited to humans, mice, Drosophila, Neurospora, plants, and cyanobacteria) identified many circadian genes as well as their protein sequences. Coupled with PCR methods to bootstrap from one system to another (e.g., [2,3]), this strategy also revealed that many clock proteins are shared between systems. For example, mammals and Drosophila use orthologs to construct their clocks [4-6]. Fly proteins include the PAS domain-containing transcription factor heterodimer Clock-Cycle (CLK-CYC [orthologs in mammals: CLK-BMAL1]) and the negative regulator Period (PER [orthologs in mammals: PER1, PER2]). These relationships indicate that a similar, basic clock mechanism was present in a common ancestor, before the separation of insects and mammals more than 500 million years ago. Some argue that the relationship of basic clock mechanism and proteins extends to Neurospora [7,8], which would push back the common ancestor date even further. (I am assuming that horizontal gene transfer is not responsible for the commonalities between systems.)
There is, however, no evidence that this relationship extends across the animal-bacterial kingdom divide; i.e., the key circadian proteins of mammals appear completely unrelated to the key circadian proteins of cyanobacteria. Although negative evidence must be interpreted with great caution ("absence of evidence is not evidence of absence"), there is no relationship evident between the circadian proteins of cyanobacteria and those of mammals [4,9]. As this is not the case for many other classes of proteins, the strong suggestion is that circadian rhythms have arisen at least twice, once in an ancestor of present-day cyanobacteria and then again in an ancestor of animals. (More than two evolutionary origins are also possible, as the different set of plant circadian proteins may indicate a third independent origin; although see below.) As some early version of cyanobacteria are generally credited with the rise of oxygen about 2.4 billion years ago, and multicellular eukaryotes did not appear for another 1.5 billion years or so [10], the evolution of cyanobacterial rhythms was probably well before that of eukaryotic rhythms.
The Importance of Biochemistry
A multiple-origin view of circadian clock origins has implications for how animal clocks keep time; i.e., what are their mechanisms or "quartz crystals"? In other words, progress in one system may have no impact on understanding a second. Relevant also is the fact that genetics is a poor way to define mechanism, in contrast to its irrefutable value in identifying key genes and proteins. These sequences are seductive, as a link between a circadian gene and a transcription factor can be interpreted to indicate an intimate relationship between transcription and timekeeping (e.g., [11]). However, only biochemistry can rigorously define mechanism, and nowhere is the distinction with genetics better illustrated than in the breathtaking reconstruction of a cyanobacterial clock in vitro [12].
Exploring the 'Global Workspace' of Consciousness:
As an explanatory principle in biology, vitalism has long been in decline, as one discovery after another revealed that mechanisms provide convincing explanations--hearts are pumps, genes are code--for all manner of life's phenomena. But even through the 20th century, the mind has been vitalism's last redoubt, because there has been no simple, satisfactory, mechanistic explanation of the most puzzling aspect of the mind: the nature of conscious awareness. For many years, even asking questions about the inner workings of this mental black box was taboo among some groups of scientists.
But that has all changed. A flood of new discoveries in every area of neuroscience has led to competing models of consciousness, and most importantly, testable hypotheses. A new study by Raphael Gaillard, Lionel Naccache, and colleagues provides support for one such model by showing that conscious, but not nonconscious, visual information is rapidly and widely distributed across the brain, provoking the synchronized brain activity that is the hallmark of conscious processing.
In a cohort study in this month's PLoS Medicine, Nav Kapur (University of Manchester, United Kingdom) and colleagues report that young men (24 years and under) who had left the UK Armed Forces were at higher risk of suicide than either young men in the general population or those still in active service [1]. The risk appeared to be greatest in the first two years after discharge, in those with a short length of service, and in those of lower rank. There was a low rate of contact with mental health specialists in the year before death--just 14% for those under 20 years and 20% for those under 24 years. This study has identified a vulnerable group and highlights the need for targeted intervention to save lives.
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