Fig. 5.

Proposed scenarios of the circadian clock evolution in Bilateria. In the Drosophila ancestor, loss of cry-m gene resulted in a feedback loop relying on a PER + TIM-d dimer with CRY-d serving for light-mediated resetting of the system (Ceriani et al. 1999). A two-step process, when TIM-d first became a modulator of the τ, and only when it was lost, it allowed for a smooth transition to the PER + CRY-m system, with a functional clock in each step. In P. apterus, TIM-d is still present as a modulator of the clock, whereas CRY-d is absent. However, the timing of cry-d loss might differ between lineages. In one scenario, TIM-d could become a modulator in the presence of CRY-d, which would be lost afterward (situation observed in P. apterus). In the second scenario, the modulatory role of TIM-d led to its loss, excluding CRY-d from the loop and resulting in its subsequent loss. The involvement of TIM-m in the circadian clock is indicated both from mammalian models (Barnes et al. 2003; Kurien et al. 2019) and insect models (Benna et al. 2010; Nose et al. 2017), albeit its role is not established in detail. The third type of path observed in evolution involves the loss of the per gene. This strikingly unusual clock found in two basal deuterostomian phyla, Hemichordata, and Echinodermata, is apparently functional (Peres et al. 2014), although the mechanism remains unknown.