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Ancestral sequence reconstruction is a technique of growing importance in molecular biology and comparative genomics. As a powerful technique for both testing evolutionary and ecological hypotheses as well as uncovering the link between sequence and molecular phenotype, there are potential applications in a number of fields.
Beginning with a historical overview of the field including applications, the discussion then moves into potential applications in drug discovery and the pharmaceutical industry. A section on computational methodology provides a detailed discussion on available methods for reconstructing ancestral sequences, including advantages, disadvantages, and potential pitfalls. Purely computational applications, including whole proteome reconstruction are discussed. Another section provides a detailed discussion on taking computationally reconstructed sequences and synthesizing them in the laboratory, while the last section describes scientific questions where experimental ancestral sequence reconstruction has been utilized to provide insights.
All together, this book provides an overarching scientific vision of the power of ancestral sequence reconstruction coupled to a computational and experimental how-to guide, while simultaneously addressing some of the hot topics in the field.
1. The Early Days of Paleogenomics, Connecting Molecules to the Planet; 2. Ancestral Sequence Reconstruction as a Tool to Understand Natural History and Guide Synthetic Biology: Realizing and Extending the Vision of Zuckerkandl and Pauling; 3. Linking Sequence to Function in Drug Design with Ancestral Sequence Reconstruction; 4. Probabilistic Models and Their Impact on the Accuracy of Reconstructed Ancestral Sequences; 5. Probabilistic Ancestral Sequences Based on the Markovian Model of Evolution- Algorithms and Applications; 6. Estimating the History of Mutations on a Phylogeny; 7. Coarse Projections of the Protein-Mutational Fitness Landscape; 8. Dealing with Uncertainty in Ancestral Sequence Reconstruction: Sampling from the Posterior Distribution; 9. Evolutionary Properties of Sequences and Ancestral State Reconstruction; 10. Reconstructing the Ancestral Eukaryote- Lessons from the Past; 11. Using Ancestral Sequence Inference to Determine the Trend of Functional Divergence After Gene Duplication; 12. Reconstruction of Ancestral Proteomes; 13. Computational Reconstruction of Ancestral Genomic Regions from Evolutionarily Conserved Gene Clusters; 14. Experimental Resurrection of Ancient Biomolecules: Gene Synthesis, Heterologous Protein Expression, and Functional Assays; 15. Dealing with Model Uncertainty in Reconstructing Ancestral Proteins in the Laboratory: Examples from Ancestral Visual Pigments and GFP-like Proteins; 16. Unraveling the Evolution of Complexity by Resurrecting Ancient Genes; 17. A Thermophilic Last Universal Ancestor Inferred from its Estimated Amino Acid Composition; 18. The Resurrection of Ribonucleases from Mammals. From Ecology to Medicine; 19. Evolution of Specificity and Diversity
