Rotary Clock Discovered in Bacteria

A biochemist has discovered one in the simplest of organisms, one-celled cyanobacteria. Examining the three complex protein components of its circadian clock, he thinks he has hit on a model that explains its structure and function: it rotates to keep time. Though it keeps good time, this clock is only about 10 billionths of a meter tall.
Scientists have known the parts of the cyanobacterial clock. They are named KaiA, KaiB, and KaiC. Jimin Wang of the Department of Molecular Biophysics and Biochemistry at Yale, publishing in Structure,¹ has found an elegant solution to how the parts interact. He was inspired by the similarity of these parts to those in ATP synthase (see 04/30/2005 entry), a universal enzyme known as a rotary motor. Though structurally different, the Kai proteins appear to operate as another rotary motor – this time, a clock.
We learned last time (see 09/15/2004 entry) that the parts interact in some way in sync with the diurnal cycle, but the mechanism was still a “black box.” Wang found that the KaiC part, a six-sided hexagonal cylinder, has a central cavity where the KaiA part can fit when it undergoes an “activation” that changes its shape, somewhat like unfolding scissors. Like a key, it fits into the central shaft and turns. The KaiB part, like a wing nut, fastens on KaiB at the bottom of the KaiC carousel. For every 120ö turn of the spindle, phosphate groups attach to the outside of the carousel, till KaiC is fully saturated, or phosphorylated. This apparently happens to multiple Kai complexes during the night.
How does this keep time? When unphosphorylated, KaiC affects the expression of genes. During the night, when complexed with the other two parts, it is repressed from acting, effectively shutting down the cell for the night. Apparently many of these complexes form and dissociate each cycle. As the complexes break up in the morning, expression resumes, and the cell wakes up. When KaiC separates from the other parts, it is destroyed, stopping its repression of genes and stimulating the creation of more KaiC. “In summary,” he says, “the Kai complexes are a rotary clock for phosphorylation, which sets the destruction pace of the night-dominant Kai complexes and timely releases KaiA.” The system sets up a day-night oscillation feedback loop that allows the bacterium keep in sync with the time of day.
Wang shares the surprise that a bacterium could have a clock that persists longer than the cell-division cycle. This means that the act of cell division does not break the clock:

“There is no mention of evolution in this paper.” The inverse law of Darwinese stands: the more detailed the discussion of cellular complexity, the less the tendency to mention evolution.

Or it could be because this was published only two years ago. The problem with making generalizations outside one's field is that someone who is a little more familiar with the literature will generally come along and shoot it all down.

Oh, BTW, hi everyone!

Abstract: Origin and evolution of circadian clock genes in prokaryotes.

Dvornyk V, Vinogradova O, Nevo E.

Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel.

Regulation of physiological functions with approximate daily periodicity, or circadian rhythms, is a characteristic feature of eukaryotes. Until recently, cyanobacteria were the only prokaryotes reported to possess circadian rhythmicity. It is controlled by a cluster of three genes: kaiA, kaiB, and kaiC. Using sequence data of approximately 70 complete prokaryotic genomes from the various public depositories, we show here that the kai genes and their homologs have quite a different evolutionary history and occur in Archaea and Proteobacteria as well. Among the three genes, kaiC is evolutionarily the oldest, and kaiA is the youngest and likely evolved only in cyanobacteria. Our data suggest that the prokaryotic circadian pacemakers have evolved in parallel with the geological history of the earth, and that natural selection, multiple lateral transfers, and gene duplications and losses have been the major factors shaping their evolution.

Glad to see National Science Foundation is finally supporting creation science.

New findings have circadian clock research ticking along
September 24, 2004

Martin Egli, Ph.D., and colleagues including Carl H. Johnson, Ph.D., recently solved the structure (shown on screen) of a biological clock protein in a blue-green algae. Photo by Daniel Dubois

by Leigh MacMillan
If you’ve ever suffered jet lag while traveling, you can blame your circadian clock. These molecular timepieces synchronize our sleep-wake cycles — and a host of other physiological routines — with the external environment’s daily rhythm.
Out-of-sync clocks cause jet lag, make shift work difficult, and have been linked to sleep disorders, some forms of depression, and even cancer.
A flurry of recent research findings is now advancing our understanding of circadian clocks and could ultimately lead to novel treatments for clock-related disorders. Vanderbilt investigators Martin Egli, Ph.D., associate professor of Biochemistry, and Carl H. Johnson, Ph.D., professor of Biological Sciences, teamed to solve the structure of a clock protein in cyanobacteria, more commonly known as blue-green algae.
Blue-green algae are the simplest organism known to have biological clocks. As in higher organisms, like human beings, the clocks in cyanobacteria regulate gene expression, cyclically turning genes on and off. Three proteins — KaiA, KaiB, and KaiC, named after the Japanese word for cycle — are the key components of the cyanobacterial clock; without any one of them, the clock does not keep time.
Egli and Johnson published the crystal structure — a kind of molecular “snapshot” — of KaiC last month in Molecular Cell and reported additional features of the protein this week in the Proceedings of the National Academy of Sciences.
Though the proteins that make up the gears and springs of the circadian clock in cyanobacteria differ from those that form the human clock, the fundamental biochemistry of clock function may be conserved, the investigators said.
“Hopefully some of the basic principles that we uncover at the biochemical level [in cyanobacteria] will guide the research in the mammalian systems,” Johnson said.
Other investigators have published structures of KaiA and KaiB in recent months, putting the field in a position to tackle complex questions of clock function, Egli said. “There’s been this culmination of five years worth of work, all in a matter of months. It’s a really exciting time.”
The KaiC structure is already providing hints to its biochemical operations, but the investigators stressed that the work is still in an early stage.
“Even though we’ve learned things from the structure,” Egli said, “the big question still is: what are the underlying biochemical mechanisms that allow organisms to control their rhythms so precisely?”
Six KaiC molecules appear to group together, into a ring-like structure that looks something like a mechanical gear — oddly appropriate, given its function as the core of the timepiece. KaiA and KaiB associate with the KaiC ring depending on a biochemical reaction called phosphorylation. Egli and Johnson’s work has identified three phosphorylation sites on KaiC; mutation of any of these sites turns off the clock.
The KaiC structure reveals unexpected evolutionary relationships to proteins that manufacture the energy molecule ATP and to DNA pumps. What these similarities mean is still anyone’s best guess, Egli said. But armed with the structures of all three Kai proteins, investigators are poised to make progress at solving how the cyanobacterial clock keeps time.
“I think there must be some unusual mechanism,” Egli said.
In addition to potentially offering new avenues for treating some sleep disorders and forms of depression, clock research raises questions about timing of medication dosing. There may be optimum times of day for hitting a particular target, depending on the cycling of genes on and off. Other groups are investigating whether the timing of chemotherapy, for example, can reduce side effects and enhance efficacy, Egli said.
Circadian clocks, the researchers said, are increasingly being recognized as fundamental to biology.
“The emerging idea is that the organism is basically a clock shop — that everything is oscillating,” Johnson said. “The function of the brain then, specifically certain parts of the brain, is to keep all of that organized and synchronized. The brain acts as a pacemaker for all of the other clocks in all of the other cells in the body, even in your big toe.”
The research was supported by the National Institutes of Health, the National Science Foundation, and a VUMC Intramural Discovery Grant.

I still haven't seen a satisfactory explantion for the pointed tetrahedral apex in the honeycomb where the displacement is approximately 35% of the length of the side of the hexagon (this results in a local minimum on the area). Bees doing calculus just doesn't cut it for me.

Local minima (or maxima, depending) occur naturally all the time, just due to the way that various forces or processes interact. For example, soap bubbles are spherical -- minimizing the surface area for the volume of air included -- because that's what happens when the surface tension at every point pulls surrounding portions of the bubble surface towards each other. Because the surface is "trying" to contract, it quickly results in a spherical shape where all the forces equalize (because the curvature is equal at all points).

A somewhat more complex manifestation of the same thing (also in soap bubbles) results in something very much like the bee's honeycombing -- whenever three soap bubbles are stuck together, there results a point between them where three planar bubble surfaces are exactly 120 degrees apart from each other (like the "joints" of a hexagonal array or honeycomb). Get enough bubbles of roughly equal size on the surface of something, and they'll naturally form a "honeycomb" configuration:

Similarly, the "dome" on each one will be the "approximately 35% of the length of the side of the hexagon", as you decribe it, which "results in a local minimum on the area". It's just the way the surface tension forces work out, the molecules don't have to "do calculus". And neither do the bees.

A lot of things that may look like "design" or "structure" often turn out to be the result of simpler processes when you take the time to learn about them. The same goes for a lot of the biological mechanisms, which is why the usual creationist method of "looks fancy to me, *must* be designed" just doesn't hold water. Especially when natural processes like evolution are *proven* producers of amazingly "clever" results, including some that are still beyond human understanding.

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