Peering Into Paleys Black Box: The Gears of the Biological Clock
William Paley’s famous “watchmaker argument” for the existence of a Designer, though intuitively logical to many, has been criticized by naturalists on the grounds that one cannot compare mechanical devices to biological ones. Biological “contrivances” might operate on totally different principles than mechanical ones made by humans we know.
Michael Behe’s 1996 book Darwin’s Black Box was built on the theme that, until recently, the living cell was a “black box” to biologists: i.e., a system whose inner workings lay hidden from us. But now with the rapid advances in molecular biology, we are finding the cell to be a complex factory of molecular machines.
These themes of Paley and Behe seemingly converge in a commentary by Susan S. Golden (Texas A&M) in PNAS about biological clocks.1 Golden works at the Center for Research on Biological Clocks in the Texas A&M Biology Department, and was struck by recent findings in two other papers in PNAS on the circadian rhythms of “primitive” blue-green algae (cyanobacteria). To her, they suggested we are opening the black box of biological clocks, and finding treasures that look remarkably familiar to the clocks we know:
A physiological black box is to a biologist what an ornately decorated package is to a small child: a mysterious treasure that promises delightful toys within. With fitting elan, a small community of scientists has ripped open the packaging of the cyanobacterial circadian clock, compiled the parts list, examined the gears, and begun to piece together the mechanism. Over the past 2 years, the 3D molecular structures have been solved for the core components of the cyanobacterial circadian clock: KaiA, KaiB, and KaiC. In a surprisingly literal analogy to mechanical timepieces, the protein that seems to be at the heart of the clock mechanism, KaiC, forms a hexameric ring that even looks like a cog: the escape wheel, perhaps. Previous work has shown that KaiC has an autophosphorylation activity, and that the presence of KaiA and KaiB modulates the extent to which KaiC is phosphorylated. In this issue of PNAS, Nishiwaki et al. biochemically identify two amino acid residues on KaiC to which phosphoryl groups covalently attach, and show the necessity in vivo of a phosphorylation-competent residue at these positions. By searching the crystal structure for evidence of phosphorylated sites, Xu et al. pinpoint a third residue that may “borrow” the phosphoryl group dynamically. Together, their work contributes richly to our understanding of what makes the gears mesh and turn to crank out a 24-h timing circuit….
Because each of these components (at minimum) is a dimer [composite of two molecular chains], KaiC is known to be a hexamer [composite of six chains], and other proteins may be present as well, the cyanobacterial clock can be thought of as an organelle unto itself: a “periodosome” that assembles and disassembles during the course of a day, defining the circadian period. (Emphasis added in all quotes.)
The term “periodosome” means “time-keeping body” – i.e., clock. Her diagram shows KaiC as a six-sided carousel to which phosphate groups and other subunits attach and detach during the diurnal cycle. The feedback between the units provides the periodicity of the clock, similar to the back-and-forth pendulum in a grandfather clock or the escape wheel in a wristwatch. How is the clock tuned to the day-night cycle? Where do the parts come together, and how do the clock gears mesh with other cellular machines? We don’t know yet; the box has just been opened.
The clocks examined in these papers are the “simple” clocks of blue-green algae, compared to the much more complex biological clocks in eukaryotes. Even about these relatively simple systems in cyanobacteria much remains to be understood, but our initial glimpses into the inner workings of a biological clock at the molecular level remind her of the delight of opening a chest of toys for the first time:
Identification of other potential components of the periodosome, intracellular localization of the clock parts, and elucidation of other potential modifications all may yield gears that are required to smoothly tick away the time and ensure that daughter cells do not run fast or slow.
The cyanobacterial clock box, no longer black, is a chest filled with bioluminescence and attractive toys. Putting together the pieces to design a clock is a tedious task, but S. elongatus is a gracious host, and the guests at the party are hard at work.
1Susan S. Golden, “Meshing the gears of the cyanobacterial circadian clock,“ Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0405623101.
Green makes no mention of evolution in this commentary, and has no need of that hypothesis. Even granting her some poetic license in her use of the clock metaphors of gears, cogs and escape wheels ticking away, who could deny that Paley, after so many years of ridicule, has been vindicated? Yes, Dick Dawkins, a watch indeed demands a Watchmaker, and if anyone is blind, it is the one ascribing blindness to the Artificer.