Molecular Fitness Landscapes from High-Coverage Sequence Profiling

The function of fitness (or molecular activity) in the space of all possible sequences is known as the fitness landscape. Evolution is a random walk on the fitness landscape, with a bias toward climbing hills. Mapping the topography of real fitness landscapes is fundamental to understanding evolutio...

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Bibliographic Details
Published in:Annual review of biophysics 2019-05, Vol.48 (1), p.1-18
Main Authors: Blanco, Celia, Janzen, Evan, Pressman, Abe, Saha, Ranajay, Chen, Irene A
Format: Article
Language:English
Subjects:
deep mutational scanning
Evolution, Molecular
fitness landscape
Genetic Fitness
High-Throughput Nucleotide Sequencing
high-throughput sequencing
Models, Genetic
Mutation
ribozyme
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Summary:The function of fitness (or molecular activity) in the space of all possible sequences is known as the fitness landscape. Evolution is a random walk on the fitness landscape, with a bias toward climbing hills. Mapping the topography of real fitness landscapes is fundamental to understanding evolution, but previous efforts were hampered by the difficulty of obtaining large, quantitative data sets. The accessibility of high-throughput sequencing (HTS) has transformed this study, enabling large-scale enumeration of fitness for many mutants and even complete sequence spaces in some cases. We review the progress of high-throughput studies in mapping molecular fitness landscapes, both in vitro and in vivo, as well as opportunities for future research. Such studies are rapidly growing in number. HTS is expected to have a profound effect on the understanding of real molecular fitness landscapes.
ISSN:1936-122X
1936-1238
DOI:10.1146/annurev-biophys-052118-115333