ScienceDaily (Feb. 27, 2008) — Heat shock protein 90 (HSP90) has a greater impact on the appearance of new traits than previously expected, according to two articles published on February 26 in the Proceedings of the National Academy of Science (PNAS) by researchers in Whitehead Member Susan Lindquist's lab and their colleagues in Christine Queitsch’s lab at Harvard University’s FAS Center for Systems Biology.

“One of the great mysteries of biology is how life could have evolved so rapidly,” says Lindquist. “This research gives at least one plausible explanation for the speed of evolution and for the evolution of complex traits affected by several genes.”

HSP90 belongs to a class of proteins called chaperones, which help other proteins in the cell fold properly, prevent protein clumping, and escort improperly made proteins to be recycled. These vital functions become even more important when a cell is stressed by heat, cold, toxins or other hardships that affect protein folding.

Hsp90 is particularly interesting because it is specialized to chaperone proteins that are key regulators of growth and development. Thus, it is in a position to couple environmental change to the release of hidden genetic variation and thereby to produce a host of new traits. Selective breeding can lead to the enrichment of those genetic changes, allowing the trait to be inherited even in the absence of stress.

“In previous studies, most of the new traits that appeared in response to stress would have been detrimental to the organism – hopeful monsters,” says Lindquist.

In the current studies, Todd Sangster and his co-authors used inbred mustard plants (Arabidopsis thaliana) and simulated stress by inhibiting their HSP90 production with the chemical geldanamycin, a known, highly specific HSP90 inhibitor or by RNAi. The authors then examined the effects of stressing the plants. When the plants were grown without geldanamycin, HSP90 suppressed the mutant proteins, so their effects were not observed and the plant appeared normal.

However, when the plants were slightly stressed by geldanamycin, HSP90-related traits emerged; seedling stem and root length increased, flowering time was delayed and size and fitness were altered. The abundance of naturally occurring genetic variation that is affected by Hsp90 was remarkable. The authors also genetically mapped the traits that could be affected by HSP90 and found that nearly every complex trait in A. thaliana that they investigated could be affected by HSP90-dependent genetic variation.

“One stressful event can affect many traits and allow previously unseen genetic variation to be expressed,” says Sangster. “We don’t know yet what is going on at the molecular level—why the HSP90-dependent traits are expressed when the plants are mildly stressed.”

Future research could include mapping HSP90-dependent traits and determining how this interaction between HSP90 and the mutant trait proteins at the molecular level.

Funding was provided by the Howard Hughes Medical Institute, the Mathers Foundation, the NIGMS grant for National Centers for Systems Biology, and the Bauer Fellowship.

Susan Lindquist’s primary affiliation is with Whitehead Institute for Biomedical Research, where her laboratory is located and all her research is conducted. She is also professor of biology at Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute.

Whitehead Institute for Biomedical Research is a nonprofit, independent research and educational institution. Wholly independent in its governance, finances and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments.

Full citation:

PNAS, February 26, 2008, 105 (7) “HSP90 affects the expression of genetic variation and developmental stability in quantitative traits” Todd A. Sangster (1,2), Neeraj Salathia (3), Soledad Undurraga (3), Kurt Schellenberg (3), Susan Lindquist (1), and Christine Queitsch (3)

1. Committee on Genetics, University of Chicago
2. Whitehead Institute for Biomedical Research
3. FAS Center for Systems Biology, Harvard University

PNAS, February 26, 2008, 105 (7) “HSP90-Buffered Genetic Variation is Common in Arabidopsis thaliana” Todd A. Sangster (1,2), Neeraj Salathia (3), Hana N. Lee (3), Etsuko Watanabe (3), Kurt Schellenberg (3), Keith Morneau (3), Hui Wang (3), Soledad Undurraga (3) , Christine Queitsch (3) and Susan Lindquist (1)

1.  Committee on Genetics, University of Chicago
2. Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute
3. FAS Center for Systems Biology, Harvard University

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