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Systematic Mapping of Protein Mutational Space

Systematic mappings of the effects of all possible mutations in a given protein sequence are routinely performed, with the aim of understanding protein structure-function and evolution. Most of these experiments indicate that the majority of amino acid substitutions are neutral. Our experimental system mimicked the manner by which protein sequences diverge in nature: a prolonged, gradual accumulation of mutations while retaining the protein¹s structure and function. Unlike previous mappings, the sequence-function Œheat map¹ derived from this experiment indicates that the fraction of deleterious mutations is in the order of 80% (dark to light blue) whereas the neutral mutations (white; ~15%), let alone beneficial mutations (~2%; in red), comprise a minority. Tawfik et al.

Image Credit: Tawfik et al.