The Discovery of Circadian Clocks in Bacteria

At the original Cold Spring Harbor Symposium on Biological Clocks (47 years ago), there was already an appreciation that microbial organisms were capable of circadian rhythmicity. That volume featured papers on circadian rhythms in the microbes Euglena (Bruce 1961), Gonyaulax (Hastings 1961; Sweeney 1961; Sweeney and Hastings 1961), and Paramecium (Ehret 1961). Several of those papers have been influential for many years. For example, the paper by J.W. Hastings on biochemical aspects has been widely cited as evidence for the relative insensitivity of circadian oscillators to drugs/chemicals (Hastings 1961). The paper by B.M. Sweeney on single Gonyaulax cells provided suggestive evidence that circadian rhythms might be a cellular phenomenon and not an emergent property of populations of cells (Sweeney 1961). And the paper by Sweeney and Hastings on temperature compensation is still cited regularly for its suggestion that temperature compensation might be mechanistically accomplished by coupled biochemical reactions (Sweeney and Hastings 1961). During the past 47 years, salient discoveries in circadian rhythmicity have used microbial organisms (Edmunds 1988; Johnson and Kondo 2001). The two eukaryotic microbes that are most commonly studied today for circadian investigations are the fungus Neurospora crassa and the green alga Chlamydomonas reinhardtii, whose circadian properties were first reported in 1959 for Neurospora (Pittendrigh et al. 1959) and in 1970 for Chlamydomonas (Bruce 1970). Undoubtedly, the reason that those two microbes have been selected for continued study is that both classical and molecular genetic approaches are possible. Nevertheless, with the increasing ability in mammalian systems to apply techniques that were heretofore only possible in microbes, coupled with the increasing pressure from funding agencies to do “translational research” rather than basic research, the interest in nonmammalian models for the study of circadian rhythms has waned somewhat. This attitude might be particularly applied to the case of bacterial model systems—the subject of this paper—because the key clock genes that are involved in prokaryotic circadian rhythms (at least, in cyanobacteria; Ishiura et al. 1998) have no homologs in the genomes of mammals, insects, or fungi, nor do the clock genes in eukaryotes have obvious homologs in bacteria. Despite that perception, however, the bacterial circadian system has in the interval of 15 years blossomed from a curiosity to one of the most important model systems—one that has enabled insights and approaches that were technically impossible elsewhere. The goal of this chapter is to briefly describe the insights resulting from the study of bacterial (especially cyanobacterial) clocks, to demonstrate what those studies have uniquely told us, and to speculate upon the future of bacterial clock studies and what they might tell us about eukaryotic clocks.