In silico mutation results.

<p>From one to six random mutations were simulated in each model 500 times. Mutants were considered viable if they correctly completed their cell cycles when analyzed with a synchronous update rule. However, mutations tended to reduce timing robustness even in the viable mutants, indicating that timing robustness is maintained by selection.</p

Fission yeast models.

<p>(A) Fission yeast model derived from Sveiczer, et al, 2004 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008906#pone.0008906-Sveiczer2" target="_blank">[23]</a>. (B) Revised speed-independent model.</p

Budding yeast models.

<p>Nodes in the graph represent molecules, complexes, etc. Arrows with pointed heads represent activation, and arrows with bars indicate inhibition. Thin arrows represent a weight of 1/3, normal arrows represent a weight of 1 and thick arrows represent weight 3. (A) The model from Li, et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008906#pone.0008906-Li1" target="_blank">[14]</a>. (B) A subset of the model that highlights the first timing hazard. Nodes with values marked with * are enabled to change. If Cdc20 transitions from 1 to 0 before Cdh1 transitions from 0 to 1, Cdh1 will stay at 0, causing the cell cycle to arrest before it has returned to G1. (C) The hazard can be eliminated by replacing Cdc20 self-degradation with inhibition of Cdc20 by Cdh1, ensuring that Cdh1 transitions to 1 before Cdc20 transitions to 0. (D) The final speed-independent model for budding yeast.</p