Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Edgar Medina used a phylogenomic approach to show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi (e.g. Spizellomyces punctatus, shown in picture). We hypothesized that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, our data show that SBF can regulate promoters with E2F binding sites in budding yeast. This was a fun and fruitful collaboration with the Skotheim and Gordan labs. You can read more about this research (“Hijacked cell division helped fuel rise of Fungi” by Robin A. Smith) at Duke Today.
Medina EM, Turner JJ, Gordan R, Skotheim JM, Buchler NE. Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi. eLife 5:e09492 (2016)
Physarum polycephalum (“many-headed slime”) is a giant amoeba with similarities to the common ancestor of amoeba, fungi and animals. Our lab helped analyze its genome to show that it has molecular features that were once thought to be specific for either animals or plants. Like animals (but unlike plants or fungi), Physarum uses tyrosine-kinase signaling for processing. Nick Buchler analyzed cell cycle regulators in Physarum and other amoeboid genomes to show that Physarum may be a better model organism than yeast and fungi for studying conserved mechanisms of cell cycle regulation in the ancestor of amoeba and animals.
Schaap P et al, The Physarum polycephalum genome reveals extensive use of prokaryotic two-component and metazoan-type tyrosine kinase signaling. Genome Biol Evol. 8: 109 (2016)
We studied the interaction of two oscillators, the cell division cycle (CDC) and yeast metabolic cycle (YMC) in budding yeast. Previous work suggested that these cycles interact to separate high oxygen consumption from DNA replication to prevent genetic damage. To test this hypothesis, Tony Burnetti grew genetically diverse strains at a number of growth rates and measured DNA replication and oxygen consumption with high temporal resolution. His data showed that high oxygen consumption is not strictly separated from DNA replication; rather, cell cycle Start was coupled with the initiation of high oxygen consumption and catabolism of storage carbohydrates. The function of this YMC-CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.
Burnetti AJ, Aydin M, Buchler NE. Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates. Mol. Biol. Cell 27: 64 (2016)