Ancestral Sequence Reconstruction

Ancestral sequence reconstruction is a technique of growing importance in molecular evolutionary biology and comparative genomics. As a powerful tool for testing evolutionary and ecological hypotheses, as well as uncovering the link between sequence and molecular phenotype, there are potential applications in a range of fields. Ancestral Sequence Reconstruction starts with a historical overview of the field, before discussing the potential applications in drug discovery and the pharmaceutical industry. This is followed by a section on computational methodology, which provides a detailed discussion of the available methods for reconstructing ancestral sequences (including their advantages, disadvantages, and potential pitfalls). Purely computational applications of the technique are then covered, including whole proteome reconstruction. Further chapters provide a detailed discussion on taking computationally reconstructed sequences and synthesizing them in the laboratory. The book concludes with a description of the scientific questions where experimental ancestral sequence reconstruction has been utilized to provide insights and inform future research. This research level text provides a first synthesis of the theories, methodologies and applications associated with ancestral sequence recognition, while simultaneously addressing many of the hot topics in the field. It will be of interest and use to both graduate students and researchers in the fields of molecular biology, molecular evolution, and evolutionary bioinformatics.

This volume presents a diverse collection of methodologies used to study various problems at the protein sequence and structure level. The chapters in this book look at issues ranging from broad concepts like protein space to specifics like antibody modeling. Topics include point mutations, gene duplication, de novo emergence of new genes, pairwise correlated mutations, ancestral protein reconstruction, homology modelling, protein stability and dynamics, and protein-protein interactions. The book also covers a wide range of computational approaches, including sequence and structure alignments, phylogenies, physics-based and mathematical approaches, machine learning, and more. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and prerequisites, step-by-step, readily reproducible computational protocols (using command line or graphical user interfaces, sometimes including computer code), and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and authoritative, Computational Methods in Protein Evolution is a valuable resource that offers useful workflows and techniques that will help both novice and expert researchers working with proteins computationally.

The primary aim of this book is to provide a synthesis of our current understanding of hemoglobin function and evolution, and to illustrate how research on one particular family of proteins has provided general insights into mechanisms of protein evolution and biochemical adaptation. In doing so, it will also promote an appreciation of how mechanistic insights into protein function can enrich our understanding of how evolution works. Reciprocally, it highlights how approaches in evolutionary genetics (such as phylogenetic comparative methods and ancestral sequence reconstruction) can be brought to bear on questions about the functional evolution of proteins. This treatise on the functional evolution of hemoglobin illustrates how research on a single, well-chosen model system can enhance our investigative acuity and bring key conceptual questions into especially sharp focus.

This book describes the models, methods and algorithms that are most useful for analysing the ever-increasing supply of molecular sequence data, with a view to furthering our understanding of the evolution of genes and genomes.

Sequence - Evolution - Function is an introduction to the computational approaches that play a critical role in the emerging new branch of biology known as functional genomics. The book provides the reader with an understanding of the principles and approaches of functional genomics and of the potential and limitations of computational and experimental approaches to genome analysis. Sequence - Evolution - Function should help bridge the "digital divide" between biologists and computer scientists, allowing biologists to better grasp the peculiarities of the emerging field of Genome Biology and to learn how to benefit from the enormous amount of sequence data available in the public databases. The book is non-technical with respect to the computer methods for genome analysis and discusses these methods from the user's viewpoint, without addressing mathematical and algorithmic details. Prior practical familiarity with the basic methods for sequence analysis is a major advantage, but a reader without such experience will be able to use the book as an introduction to these methods. This book is perfect for introductory level courses in computational methods for comparative and functional genomics.

A broad, hands on guide with detailed explanations of current methodology, relevant exercises and popular software tools.

This book presents and explains modern statistical methods and computational algorithms for the comparative analysis of genetic sequence data in the fields of molecular evolution, molecular phylogenetics, statistical phylogeography, and comparative genomics. The book offers numerous examples of real data analysis and numerical calculations to illustrate the theory, in addition to the working problems at the end of each chapter. The coverage of maximum likelihood and Bayesian methods are in particular up-to-date, comprehensive, and authoritative.