Modifiers of the Genotype-Phenotype Map: Hsp90 and Beyond.
Disruption of certain genes alters the heritable phenotypic variation among individuals. Research on the chaperone Hsp90 has played a central role in determining the genetic basis of this phenomenon, which may be important to evolution and disease. Key studies have shown that Hsp90 perturbation modifies the effects of many genetic variants throughout the genome. These modifications collectively transform the genotype-phenotype map, often resulting in a net increase or decrease in heritable phenotypic variation. Here, we summarize some of the foundational work on Hsp90 that led to these insights, discuss a framework for interpreting this research that is centered upon the standard genetics concept of epistasis, and propose major questions that future studies in this area should address.
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
Rachel
R
Schell
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
Martin
M
Mullis
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
Ian M
IM
Ehrenreich
D004843:Epistasis, Genetic; D005838:Genotype; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D012641:Selection, Genetic
D018841:HSP90 Heat-Shock Proteins