Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature.

摘要: The last decade has seen a growing number of experiments aimed at systematically mapping the effects mutations in different proteins, and attempting to correlate their biophysical biochemical with organismal fitness. While insightful, systematic laboratory measurements fitness present challenges difficulties. Here, we discuss limitations associated such measurements, particular challenge correlating single protein level ("protein fitness") on A variety experimental setups are used, some measuring direct function others monitoring growth rate model organism carrying mutants. manners by which calculated presented also vary, conclusions, including derived distributions mutations, vary accordingly. comparison natural diversity, namely amino acid changes that have fixed course millions years evolution, is debatable. results may, therefore, be less relevant understanding long-term inter-species variations yet insightful regard short-term polymorphism, for example, study human SNPs.