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Updated: Jul 13, 2026

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
The distribution of fitness effects of new mutations
Adam Eyre-Walker1, Peter D Keightley
1Centre for the Study of Evolution, University of Sussex, Brighton, BN1 9QG, UK. a.c.eyre-walker@sussex.ac.uk
Abstract:
The distribution of fitness effects (DFE) of new mutations is a fundamental entity in genetics that has implications ranging from the genetic basis of complex disease to the stability of the molecular clock. It has been studied by two different approaches: mutation accumulation and mutagenesis experiments, and the analysis of DNA sequence data. The proportion of mutations that are advantageous, effectively neutral and deleterious varies between species, and the DFE differs between coding and non-coding DNA. Despite these differences between species and genomic regions, some general principles have emerged: advantageous mutations are rare, and those that are strongly selected are exponentially distributed; and the DFE of deleterious mutations is complex and multi-modal.
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