Rory Munro

Day 16 of great biology papers. "Expression of a Gene Cluster kaiABC as a Circadian Feedback Process in Cyanobacteria." Ishiura M. et al. (1998). Three genes — kaiA, kaiB, and kaiC — encode a clock that oscillates almost perfectly in a 24-hour period. My favorite biology story of all time. ***** In 1998, two Americans and a Japanese professor (Takao Kondo) discovered a gene cluster in a cyanobacterium. This cluster encoded three genes that seemed to make proteins that act as a sort of clock. They named the cluster "kai," which means "cycle" in Japanese. For their first study, the scientists fused a luciferase gene — which encodes a protein that emits light in fireflies — to one of these clock proteins. They were then able to watch the cells literally dim and brighten throughout the day. They made a series of mutations in the kaiA, B, and C genes and studied how each alteration changed the timing of the cycles. The wildtype genes oscillated with a period of 25 hours. A few years later, in 2005, Kondo's group stripped the three Kai genes from cyanobacteria and expressed them in vitro, in a test tube. They also added a bit of ATP. Remarkably, the Kai clock continued to oscillate with a nearly perfect, 24-hour period. These oscillations were "stable despite temperature change." Later work showed: - The KaiC gene is the oldest circadian gene ever found in prokaryotes. - Cells use this clock to regulate photosynthesis, and time other cellular processes with the rising and setting sun. - KaiABC interact with each other like a feed-forward loop; KaiA phosphorylates KaiC, whereas KaiB dephosphorylates KaiC. KaiA activates the expression of KaiBC, and KaiC represses it. (See: en.wikipedia.org/wiki/Cyanob…) Original Paper (1998): science.org/doi/10.1126/scie… In Vitro Paper (2005): science.org/doi/10.1126/scie… (Sorry, I can't find full-text versions.) Image #1: Oscillations in cyanobacterial cells, as measured by luminescence, for wildtype genes and mutated versions of those genes. Image #2: In vitro oscillations of kaiC phosphorylation, from the 2005 paper. Image #3: A Synechococcus elongatus (cyanobacterium) cell.