KaiA

kaiA is a gene in the 'kaiABC' gene cluster that plays a crucial role in the regulation of bacterial circadian rhythms, such as in the cyanobacterium Synechococcus elongatus. For these bacteria, regulation of kaiA expression is critical for circadian rhythm, which determines the twenty-four-hour biological rhythm. In addition, KaiA functions with a negative feedback loop in relation with kaiB and KaiC. The kaiA gene makes KaiA protein that enhances phosphorylation of KaiC while KaiB inhibits activity of KaiA. kaiA is a gene in the 'kaiABC' gene cluster that plays a crucial role in the regulation of bacterial circadian rhythms, such as in the cyanobacterium Synechococcus elongatus. For these bacteria, regulation of kaiA expression is critical for circadian rhythm, which determines the twenty-four-hour biological rhythm. In addition, KaiA functions with a negative feedback loop in relation with kaiB and KaiC. The kaiA gene makes KaiA protein that enhances phosphorylation of KaiC while KaiB inhibits activity of KaiA. Circadian rhythms have been discovered in a diversity of organisms. These rhythms control a variety of physiological activities and help organisms to adapt to environmental conditions. Cyanobacteria are the most primitive organisms that demonstrate a circadian oscillation. Cyanobacteria clocks were first founded in Blue Green Algae with the oldest known fossils about 3.5 billion years old. Susan Golden, Carl H. Johnson and Takao Kondo were the individuals who found that the minimal cyanobacteria clock consists of 3 proteins: KaiA, KaiB, and KaiC. (Note: kai means cycle in Japanese.)The experiment performed by Kondo consisted of attaching the luciferase gene and performing mutagenesis. This was the first identification of possible genes that could reconstitute a biological clock within cyanobacteria, of which KaiA was included. Cyanobacteria were the first prokaryotes reported to have a circadian clock. For the adaptation of cyanobacteria, circadian clock genes exhibit forms of significant importance since they regulate fundamental physical processes such as regulation of nitrogen fixation, cell division, and photosynthesis. Early KaiA research was conducted in the 1998 research article, “Expression of a Gene Cluster kaiABC as a Circadian Feedback Process in Cyanobacteria,” where it details the functions of the gene cluster and KaiA in that it sustains the oscillations by enhancing Kai C expression. KaiA was discovered while studying the clock mutations in Synechococcus by using bacteria luciferase as a reporter on clock controlled gene expression. This was the first instance where scientists first proposed a mechanism and a naming system for KaiA and the kaiABC gene cluster. Researchers Masato Nakajima, Keiko Imai, Hiroshi Ito, Taeko Nishiwaki, Yoriko Murayama, Hideo Iwasaki, Tokitaka Oyama, and Takao Kondo conducted the experiment 'Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro' took KaiA, KaiB, and KaiC and put them in tube with ATP, MgCl2 and buffers only. They used radioactive ATP and the phosphorylated form of KaiC which runs a bit faster than unphosphorylated KaiC. They saw a twenty-four-hour rhythm in autohydrolyzation of KaiC. The system is also temperature compensated and was noteworthy because they only needed three proteins, including KaiA, for twenty-four-hour rhythm. Research published in the paper, “Robust and Tunable Circadian Rhythms From Differentially Sensitive Catalytic Domains,” done by Connie Phong, Joseph S. Markson, Crystal M. Wilhoite, and Michael J. Rust, shows the mathematical relationship of KaiA and KaiC where KaiA stimulates the phosphorylation of KaiC. Additionally, KaiB sequesters KaiA, which promotes KaiC dephosphorylation. In addition, “In Vitro Regulation of Circadian phosphorylation rhythm of cyanobacterial clock protein KaiC, KaiA, and KaiB,” shows the entrainment mechanism of cellular circadian clock with circadian rhythm in response to intracellular levels of KaiA and the other Kai proteins. KaiA ratios to KaiB and KaiC express a circadian rhythm and guides phosphorylation of KaiC based on KaiA ratios that can entrain in different light dark conditions. Cyanobacteria were one of the oldest organisms on earth and most successful in regards to ecological plasticity and adaptability.Dvornyk performed phylogenetic analysis of kai genes and found that the kai genes have different evolutionary histories the feedback loop that kaiA is in evolved about 1,000 Mya. Minimal amount of kaiA genes prohibits a full dating of their evolution. Since they are found only in some higher cyanobacteria, kaiA genes are the youngest in comparison to kaiB and kaiC, evolutionarily speaking. Synechococcus sp. PCC7942 has kaiA whereas P.marinus does not, even though they are closely related unicellular organisms, further demonstrating the evolutionary youth of the kaiA gene. KaiA genes are also found in the genomes of the species of the kaiC subtree, in younger clades than Prochlorococcus. Thus kaiA genes most likely arrived after the speciation of Synechococcus and Prochlorococcus, about 1,051 ± 1,16.9 and 944 ± 92.9 Mya. KaiA genes are located only in cyanobacteria with a length ranging from a filamentous cyanobacteria (Anabaena and Nostoc) to unicellular cyanobacteria (Synechoccus and Synechocytis), which are 852-900 bp longer. The KaiA genes are the least conserved amongst the kai genes. Shorter homologs of kaiA and kaiB genes match only 1 segment of their longer versions closer to the 3’ terminus, unlike kaiC genes. This implies kaiA and kaiB most likely didn’t evolve through duplication. Specifically, the kaiA gene only had a single copy. KaiA statistics: 284 amino acids;Molecular mass of 32.6 kD;Isoelectric point of 4.69.