Molecular shape evolution of cyanobacterial circadian clock protein KaiC

A primitive form of clock protein KaiC has diverged into autonomous or passive time-measuring system. Here we traced molecular shape evolution of ancestral KaiCs using X-ray solution scattering and structure prediction techniques to date this diversification. The results show that the oldest KaiC emerged approximately 3.5–2.8 billion years ago as a moderately expanded and asymmetric double-ring hexamer, and subsequently evolved over approximately 1 billion years into a compact and symmetric form essential for the self-sustained rhythmicity in extant cyanobacteria. In parallel, the oldest KaiC branched into an oligomer composed of two hexamers after approximately 0.5 billion years. It appears that this prototypical dodecamer gained a higher enzymatic activity during the next approximately 0.4 billion years and was inherited by non-cyanobacterial lineages as the passive timer capable of responding rapidly to environmental cues. Consequently, geological fluctuations over approximately 1 billion years since the earliest KaiC appeared led KaiCs into the two distinct evolutionary pathways.