Evolutionary dynamics of transcriptional and translational regulation in yeast

• Autores: William Robert Blevins
• Directores de la Tesis: María del Mar Alba Soler (dir. tes.), Lucas Carey (codir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2019
• Idioma: español
• Tribunal Calificador de la Tesis: Nikolaos Vakirlis (presid.), Marina Marcet Houben (secret.), Tanya Vavouri (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
• Materias:
  • Ciencias de la vida
• Texto completo no disponible (Saber más ...)
• Resumen

  • All living organisms respond to environmental stimuli by modulating the activity of different genes. This response can occur across many locations throughout the cell such as at the level of transcription, translation, and even post-translational modifications. Some of this variation between species is attributable to the presence or absence of lineage-specific genes. The birth of new genes via de novo emergence from previously non-genic DNA is predicted to contribute significantly to this diversity. However, much remains to be understood about the evolutionary dynamics of the process of de novo gene birth.

    To explore this question, we generated high-depth transcriptomic data for 11 species of yeast, as well as ribosome profiling and proteomics data for Saccharomyces cerevisiae in rich media and oxidative stress conditions. This dataset allowed us to investigate the differences between the transcriptomes of the same species between the two conditions as well as the differences between the 11 species. We were able to characterize the response of S. cerevisiae to severe oxidative stress at both the transcriptional level and the translational level. This revealed extensive post-transcriptional regulation, suggesting that RNA-seq data by itself is insufficient explain the up-regulation and down-regulation of genes in response to severe oxidative stress. This dataset also enabled us to approximate the point in evolutionary history where new intergenic loci began to be transcribed. We identified 213 putative de novo genes in S. cerevisiae; over a third of them are translated, and approximately half of them overlap more ancient genes on the antisense strand. We found that a significant fraction of S. cerevisiae genes (~5%) have emerged de novo over the past 20 million years.

    The thesis is divided into 7 main sections (INTRODUCTION, RESULTS, DISCUSSION, CONCLUSIONS, FUTURE RESEARCH, ANNEX, and REFERENCES) which are detailed below. The results section is composed of the three following manuscripts:

    Blevins, W. R., Ruiz-Orera, J., Messeguer, X., Blasco-Moreno, B., Villanueva-Canas, J. L., Espinar, L., Diez, J., Carey, L. and Alba, M. M. (2019) ‘Frequent birth of de novo genes in the compact yeast genome’, bioRxiv, p. 575837. doi:10.1101/575837 (Preprint uploaded on March 13th, 2019) Blevins, W. R., Carey, L. B. and Albà, M. M. (2019) ‘Transcriptomics data of 11 species of yeast identically grown in rich media and oxidative stress conditions’, BMC Research Notes, 12(1), p. 250. doi:10.1186/s13104-019 4286-0 (Published on May 3rd, 2019) Blevins, W. R., Tavella, T., Moro, S. G., Blasco-Moreno, B., Closa-Mosquera, A., Díez, J., Carey, L. B. and Albà, M. M. (2019) ‘Extensive post-transcriptional buffering of gene expression in the response to severe oxidative stress in baker’s yeast’, Scientific Reports, 9(1), p. 11005. doi: 10.1038/s41598-019-47424-w (Published on July 29th, 2019) Thesis Table of Contents:

    1. INTRODUCTION 1.1 A brief history of a ‘simple’ model organism 1.1.1 Evolutionary origins 1.1.2 Genome assembly and annotation 1.2 Sequencing technologies 1.2.1 First, second, and third generation sequencing 1.2.2 Transcriptome sequencing 1.2.3 Translatome sequencing 1.2.4 Proteome sequencing 1.3 Characteristics of S. cerevisiae 1.3.1 Lifestyle 1.3.2 Genome composition 1.3.3 Gene regulation 1.3.4 Response to oxidative stress 1.4 The life cycle of genes 1.4.1 Making genes from other genes 1.4.2 De novo gene birth 1.4.3 Identifying and classifying new genes 2. RESULTS 2.1 Transcriptomics data of 11 species of yeast identically grown in rich media and oxidative stress conditions 2.1.1 Abstract 2.1.2 Objective 2.1.3 Data description 2.1.4 Limitations 2.1.5 Acknowledgments 2.1.6 Authors’ contributions 2.1.7 Additional information 2.2 Frequent birth of de novo genes in the compact yeast genome 2.2.1 Abstract 2.2.2 Background 2.2.3 Results 2.2.4 Discussion 2.2.5 Methods 2.2.6 Acknowledgments 2.2.7 Authors’ contributions 2.3.6 Additional information 2.3 Extensive post-transcriptional buffering of gene expression in the response to severe oxidative stress in baker’s yeast 2.3.1 Abstract 2.3.2 Introduction 2.3.3 Results 2.3.4 Discussion 2.3.4 Methods 2.3.5 Data Availability 2.3.5 Acknowledgments 2.3.6 Author Contributions 2.3.6 Additional Information 3. DISCUSSION 3.1 Measuring gene regulation 3.2 Where do de novo genes come from? 3.3 How to identify de novo genes 4. CONCLUSIONS 5. FUTURE RESEARCH 6. ANNEX 6.1 Journal articles 6.2 Oral presentations 6.3 Poster presentations 6.4 Science communication and outreach 7. REFERENCES