Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here.

Cooperative and sequence-dependent model for RNAP dynamics: Application to ribosomal gene transcription.

Escherichia coli ribosomal genes are a well-established experimental model used to investigate the transcription process. These genes are essential to cell physiology and are therefore strongly expressed. Multiple transcription units collaborate in rrn expression. Experiments involving electron microscopy have shown the non-uniform density of the RNA polymerases transcribing these ribosomal operons. Here, we investigate RNAP collaborative transcription in E. coli ribosomal genes using a stochastic sequence-dependent model that included interactions among the RNAPs. We achieved results consistent with experimental data using a model with variable parametrization for genic and intergenic regions, compared with previous attempts that used uniform parameters for genic and intergenic regions. Our model also showed that cooperative behaviour reduced the dwell times in pause sites predicted by the single-round approach but induced a new pausing event at an upstream position. This work may stimulate new experimental research and provide other scenarios to test our model predictions.

Intersex, Hermaphroditism, and Gonadal Plasticity in Vertebrates: Evolution of the Müllerian Duct and Amh/Amhr2 Signaling.

In vertebrates, sex organs are generally specialized to perform a male or female reproductive role. Acquisition of the Müllerian duct, which gives rise to the oviduct, together with emergence of the Amh/Amhr2 system favored evolution of viviparity in jawed vertebrates. Species with high sex-specific reproductive adaptations have less potential to sex reverse, making intersex a nonfunctional condition. Teleosts, the only vertebrate group in which hermaphroditism evolved as a natural reproductive strategy, lost the Müllerian duct during evolution. They developed for gamete release complete independence from the urinary system, creating optimal anatomic and developmental preconditions for physiological sex change. The common and probably ancestral role of Amh is related to survival and proliferation of germ cells in early and adult gonads of both sexes rather than induction of Müllerian duct regression. The relationship between germ cell maintenance and sex differentiation is most evident in species in which Amh became the master male sex-determining gene.

Dimerization and Transactivation Domains as Candidates for Functional Modulation and Diversity of Sox9.

Sox9 plays an important role in a large variety of developmental pathways in vertebrates. It is composed of three domains: high-mobility group box (HMG box), dimerization (DIM) and transactivation (TAD). One of the main processes for regulation and variability of the pathways involving Sox9 is the self-gene expression regulation of Sox9. However, the subsequent roles of the Sox9 domains can also generate regulatory modulations. Studies have shown that TADs can bind to different types of proteins and its function seems to be influenced by DIM. Therefore, we hypothesized that both domains are directly associated and can be responsible for the functional variability of Sox9. We applied a method based on a broad phylogenetic context, using sequences of the HMG box domain, to ensure the homology of all the Sox9 copies used herein. The data obtained included 4,921 sequences relative to 657 metazoan species. Based on coevolutionary and selective pressure analyses of the Sox9 sequences, we observed coevolutions involving DIM and TADs. These data, along with the experimental data from literature, indicate a functional relationship between these domains. Moreover, DIM and TADs may be responsible for the functional plasticity of Sox9 because they are more tolerant for molecular changes (higher Ka/Ks ratio than the HMG box domain). This tolerance could allow a differential regulation of target genes or promote novel targets during transcriptional activation. In conclusion, we suggest that DIM and TADs functional association may regulate differentially the target genes or even promote novel targets during transcription activation mediated by Sox9 paralogs, contributing to the subfunctionalization of Sox9a and Sox9b in teleosts.