Hsp - 90 and

Background: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different freeliving or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints. Results: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GAbinding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not. Conclusion: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin. Background Heat shock protein 90 (Hsp-90) is essential in all eukaryotes because of its role in chaperoning proteins such as kinases, growth factors and other signal transduction proteins [1]. As knock out of hsp-90 is generally lethal, specific inhibitors have been important for defining the cellular functions of Hsp-90. Of these, the best characterised is geldanamycin (GA) a naturally occurring ansamycin compound produced by Streptomyces hygroscopicus [2]. The mode of action of GA is well documented and the crystal structure of yeast Hsp-90 complexed to GA has been solved [3]. Most eukaryotic Hsp-90s are susceptible to inhibition with GA and will bind the drug in pull-down assays using GA linked to a solid support [4]. The excepPublished: 22 October 2009 BMC Evolutionary Biology 2009, 9:254 doi:10.1186/1471-2148-9-254 Received: 9 July 2009 Accepted: 22 October 2009 This article is available from: http://www.biomedcentral.com/1471-2148/9/254 © 2009 Him et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.