Genotype to Phenotype to Fitness in the Cyanobacterial Circadian Clock

How does evolution produce complex and fine-tuned systems? It is not well understood how random genetic variation maps to function and how that function maps to fitness, especially in networks of many interacting components. In our model system, the cyanobacterial circadian clock, we’ve created a deep mutational scan and assayed the clock phenotype of over 10,000 variants. This shows that clock properties like period and amplitude are factorized and tunable, with different proteins accessing different phenotypes. We also observe constraints on the system, such as a pseudo-1D relationship between period and phase for high amplitude mutants. This data allows us to map the local phenotype landscape and we are now poised to examine fitness effects of this library.