Evolution of networks and sequences in eukaryotic cell cycle control

Abstract

The molecular networks regulating the G1 -S transition in budding yeast and mammals are strikingly similar in network structure. However, many of the individual proteins performing similar network roles appear to have unrelated amino acid sequences, suggesting either extremely rapid sequence evolution, or true polyphyly of proteins carrying out identical network roles. A yeast/ mammal comparison suggests that network topology, and its associated dynamic properties, rather than regulatory proteins themselves may be the most important elements conserved through evolution. However, recent deep phylogenetic studies show that fungal and animal lineages are relatively closely related in the opisthokont branch of eukaryotes. The presence in plants of cell cycle regulators such as Rb, E2F and cyclins A and D, that appear lost in yeast, suggests cell cycle control in the last common ancestor of the eukaryotes was implemented with this set of regulatory proteins. Forward genetics in non-opisthokonts, such as plants or their green algal relatives, will provide direct information on cell cycle control in these organisms, and may elucidate the potentially more complex cell cycle control network of the last common eukaryotic ancestor.

Evolutionary layering and the limits to cellular perfection

“…First, replication fidelities of DNA polymerases are lower in taxa with smaller effective population sizes, and also lower for enzymes involved in fewer nucleotide transactions per cell cycle, which presumably reduces the intensity of selection associated with error propagation (5). Second, although the restriction of licensing of DNA replication origins to one event per cell cycle is critical to maintaining genome integrity, there is substantial variation among eukaryotic lineages in the mechanisms regulating such behavior (26,27). As redundant mechanisms of replication licensing control appear to be common within species, these observations are consistent with the concept of evolutionary layering and random wandering of independent lineages over a multivariate drift barrier.…”

Topology and Control of the Cell-Cycle-Regulated Transcriptional Circuitry

“…This is well illustrated by analysis of the transcriptional machinery regulating the G1/S gene clusters of fungi and mammals (reviewed by Wittenberg and Reed 2005;Cross et al 2011;Bertoli et al 2013b). The activating members of the E2F family of transcriptional regulators, E2F1 being the best studied, exhibit many parallels with SBF ( Figure 6) (Dimova and Dyson 2005).…”

“…This general topic has been extensively reviewed (Bähler 2005;Wittenberg and Reed 2005;McInerny 2011) and indepth reviews covering specific transcription factor families and cell-cycle-regulated gene clusters have been presented (Murakami et al 2010;Cross et al 2011;Eriksson et al 2012). We will introduce the constituents and regulatory logic of the cell-cycle transcriptional circuitry with discussion weighted toward more recent contributions.…”

3,6‐Epidioxy‐1,10‐bisaboladiene inhibits G1‐specific transcription through Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast

“…Progression of the cell cycle from G 1 to S and from G 2 to M is promoted by CDK/cyclin complexes [6][7][8].…”

“…Transcriptional regulatory networks are evolutionarily conserved from yeast to animals [6][7][8]. Eukaryotic cells generally commit to proceeding through the cell cycle in the late G 1 phase.…”