Christine Queitsch

We are studying the causes, effects and implications of Hsp90-mediated genetic "capacitance". The molecular chaperone Hsp90 assists the maturation of many key regulatory proteins. As a result, genetic variation can accumulate in genomes and remain phenotypically silent until Hsp90 function is challenged by modest environmental change, by mutation, or by pharmacological inhibition. The existence of diverse cryptic polymorphisms with a plausible exposure mechanism may have implications for organismic plasticity and evolutionary processes.

The release of hidden genetic polymorphisms through interference with Hsp90 function has been empirically demonstrated in the evolutionarily distant lineages of plants and fruit flies. However, neither the identity of "buffered" genetic polymorphisms nor their frequency in natural populations has been determined. We are mapping naturally existing Hsp90-buffered polymorphisms for hypocotyl (stem) length in segregating populations of the plant Arabidopsis thaliana, using the drug geldanamycin to inhibit Hsp90. Our study revealed two novel genomic regions (quantitative trait loci, QTLs) contributing to hypocotyl length. Current mapping efforts center on a small interval of ~0.2 Mb on chromosome 2.

Studies using geldanamycin are limited by the drug's sensitivity to light. Therefore, in collaboration with Todd Sangster and Susan Lindquist (Whitehead Institute), we have used RNA interference to create diverse recombinant inbred lines (RILs) that are stably genetically reduced in Hsp90. These RILs are currently genotyped with an affordable array-based approach that we developed in collaboration with Duccio Cavalieri (University of Florence) and George Jander (Boyce Thompson Institute). Preliminary data, based on a subset of RILs and PCR-produced low-density maps, indicate that Hsp90 buffers many different genomic regions involved in life-history traits such as flowering time and number of siliques (seed-containing organs).

Once high-density maps are established, the complete Hsp90-reduced RIL set (200 Hsp90-reduced, 200 controls) will enable us to test a multitude of phenotypic traits for buffered QTLs, assess their frequency on a global scale, and identify buffered polymorphisms via fine-mapping.

Queitsch Lab