Project description:BACKGROUND:Gene expression is a dynamic trait, and the evolution of gene regulation can dramatically alter the timing of gene expression without greatly affecting mean expression levels. Moreover, modules of co-regulated genes may exhibit coordinated shifts in expression timing patterns during evolutionary divergence. Here, we examined transcriptome evolution in the dynamical context of the budding yeast cell-division cycle, to investigate the extent of divergence in expression timing and the regulatory architecture underlying timing evolution. RESULTS:Using a custom microarray platform, we obtained 378 measurements for 6,263 genes over 18 timepoints of the cell-division cycle in nine strains of S. cerevisiae and one strain of S. paradoxus. Most genes show significant divergence in expression dynamics at all scales of transcriptome organization, suggesting broad potential for timing changes. A model test comparing expression level evolution versus timing evolution revealed a better fit with timing evolution for 82% of genes. Analysis of shared patterns of timing evolution suggests the existence of seven dynamically-autonomous modules, each of which shows coherent evolutionary timing changes. Analysis of transcription factors associated with these gene modules suggests a modular pleiotropic source of divergence in expression timing. CONCLUSIONS:We propose that transcriptome evolution may generally entail changes in timing (heterochrony) rather than changes in levels (heterometry) of expression. Evolution of gene expression dynamics may involve modular changes in timing control mediated by module-specific transcription factors. We hypothesize that genome-wide gene regulation may utilize a general architecture comprised of multiple semi-autonomous event timelines, whose superposition could produce combinatorial complexity in timing control patterns.
Project description:45 genome-wide microarray measurements for 23 mutation accumulation lines grown in YPD liquid culture MA lines obtained by single-colony transfer on YPD plates for 600 generations, starting from a BY4741 derived strain (see Zeyl C, DeVisser JA: Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae. Genetics 2001, 157:53â61) Two biological replicates for each strain in a common reference design (no dye-swap)
Project description:Multi-genome, time series transcriptome measurements across the budding yeast cell cycle 378 genome-wide microarray measurements, 18 timepoints, nine strains of S. cerevisiae and one strain of S. paradoxus Dye-swap technical replication at each strain,timepoint pair in a common reference design
Project description:Multi-genome, time series transcriptome measurements across the budding yeast cell cycle 378 genome-wide microarray measurements, 18 timepoints, nine strains of S. cerevisiae and one strain of S. paradoxus
Project description:45 genome-wide microarray measurements for 23 mutation accumulation lines grown in YPD liquid culture MA lines obtained by single-colony transfer on YPD plates for 600 generations, starting from a BY4741 derived strain (see Zeyl C, DeVisser JA: Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae. Genetics 2001, 157:53–61)
Project description:Convergent evolution is central in the origins of multicellularity. Identifying the basis for convergent multicellular evolution is challenging because of the diverse evolutionary origins and environments involved. Haploid Kluyveromyces lactis populations evolve multicellularity during selection for increased settling in liquid media. Strong genomic and phenotypic convergence is observed between K. lactis and previously selected S. cerevisiae populations under similar selection, despite their >100-million-year divergence. We find K. lactis multicellularity is conferred by mutations in genes ACE2 or AIM44, with ACE2 being predominant. They are a subset of the six genes involved in the S. cerevisiae multicellularity. Both ACE2 and AIM44 regulate cell division, indicating that the genetic convergence is likely due to conserved cellular replication mechanisms. Complex population dynamics involving multiple ACE2/AIM44 genotypes are found in most K. lactis lineages. The results show common ancestry and natural selection shape convergence while chance and contingency determine the degree of divergence.
Project description:We describe the DNA replication timing programs of 14 yeast mutants with an extended S phase identified by a novel genome-wide screen. These mutants are associated with the DNA replication machinery, cell-cycle control, and dNTP synthesis and affect different parts of S phase. In 13 of the mutants, origin activation time scales with the duration of S phase. A limited number of origins become inactive in these strains, with inactive origins characterized by small replicons and distributed throughout S phase. In sharp contrast, cells deleted of MRC1, a gene implicated in replication fork stabilization and in the replication checkpoint pathway, maintained wild-type firing times despite over twofold lengthening of S phase. Numerous dormant origins were activated in this mutant. Our data suggest that most perturbations that lengthen S phase affect the entire program of replication timing, rather than a specific subset of origins, maintaining the relative order of origin firing time and delaying firing with relative proportions. Mrc1 emerges as a regulator of this robustness of the replication program.