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• W2137682788 abstract "Identifying mechanisms of molecular adaptation can provide important insights into the process of phenotypic evolution, but it can be exceedingly difficult to quantify the phenotypic effects of specific mutational changes. To verify the adaptive significance of genetically based changes in protein function, it is necessary to document functional differences between the products of derived and wild-type alleles and to demonstrate that such differences impinge on higher-level physiological processes (and ultimately, fitness). In the case of metabolic enzymes, this requires documenting in vivo differences in reaction rate that give rise to differences in flux through the pathway in which the enzymes function. These measured differences in pathway flux should then give rise to differences in cellular or systemic physiology that affect fitness-related variation in whole-organism performance. Efforts to establish these causal connections between genotype, phenotype, and fitness require experiments that carefully control for environmental variation and background genetic variation. Here, we discuss experimental approaches to evaluate the contributions of amino-acid mutations to adaptive phenotypic change. We discuss conceptual and methodological issues associated with in vitro and in vivo studies of protein function, and the evolutionary insights that can be gleaned from such studies. We also discuss the importance of isolating the effects of individual mutations to distinguish between positively selected substitutions that directly contribute to improvements in protein function versus positively selected, compensatory substitutions that mitigate negative pleiotropic effects of antecedent changes." @default.
• W2137682788 created "2016-06-24" @default.
• W2137682788 creator A5026872382 @default.
• W2137682788 creator A5069226961 @default.
• W2137682788 date "2011-07-08" @default.
• W2137682788 modified "2023-09-25" @default.
• W2137682788 title "Experimental Approaches to Evaluate the Contributions of Candidate Protein-Coding Mutations to Phenotypic Evolution" @default.
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• W2137682788 doi "https://doi.org/10.1007/978-1-61779-228-1_22" @default.
• W2137682788 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4409679" @default.
• W2137682788 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22065450" @default.
• W2137682788 hasPublicationYear "2011" @default.
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