The Cyanobacteria Timepiece Rings Familiar

Humans have invented a myriad of timepieces, from pendulums to oscillating atoms. Mother Nature, however, seems early on to have hit on one good design for the molecular clocks that govern circadian rhythms and used it repeatedly. Researchers report in the current Science that blue-green algae use a clock similar in form to that found in other organisms. The proteins used to keep time are different, however, suggesting that today's clocks may have arisen from at least two different biological ancestors.

At the core of all known molecular clocks is a genetic oscillator, in which a gene produces a protein that accumulates for a while and then feeds back and turns off the gene, causing the protein's concentration to oscillate over a roughly 24-hour cycle. Researchers knew that blue-green algae, or cyanobacteria, need some mechanism to pace the 24-hour cycles of nitrogen fixation and amino acid uptake crucial for life.

To identify the cyanobacterial clock proteins, Masahiro Ishiura and Takao Kondo at Nagoya University in Japan and their colleagues isolated more than 100 strains with mutations that either abolished or altered the organism's daily activity cycles. The researchers identified the mutated genes by chopping up the cyanobacterial genome and searching for pieces that would restore the normal rhythms when introduced into the mutant bacteria. They found one DNA segment, containing three genes the team called kaiA, -B, and -C--"kai" is Japanese for "cycle"--that could restore all the mutants tested.

When the team took a closer look at the clock gene activity patterns, they saw a familiar picture. KaiA protein turns up the kaiB and -C genes, while KaiC protein turns them down. This suggested a scenario in which, early in the day, the kai genes begin to produce RNA that is translated into protein. As KaiA protein accumulates, it turns up the activity of the kaiB and -C genes. Then after a delay, KaiC begins to exert the opposite effect, turning the kaiB and -C genes off. Once that happens, KaiB and -C protein levels fall, KaiC stops repressing the genes, and they come on again. If the model is right, "regulation of the clock genes is analogous" to the three other known clock systems--in fruit flies, mammals, and the bread mold Neurospora--Ishiura says, but the proteins used are completely different.

The cyanobacteria discovery is "the best evidence yet for [clocks'] independent evolution," says Northwestern University clock researcher Joe Takahashi. It could be that the same design has arisen multiple times because feedback mechanisms already in place for protein regulation provide convenient clock building blocks. Or, speculates clock researcher Michael Young of Rockefeller University, "maybe this is the only way you can make a clock."