Hsp-90 and the biology of nematodes.
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 free-living 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 GA-binding. 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.


CONCLUSIONS
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.
Him
Nik A I I N
NA
Parasitology Group, Institute of Comparative Medicine, School of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK. 0607576i@student.gla.ac.uk
Gillan
Victoria
V
Emes
Richard D
RD
Maitland
Kirsty
K
Devaney
Eileen
E
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D017238:Genes, Helminth; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000378:metabolism*; D009348:Nematoda / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D017422:Sequence Analysis, DNA
D016227:Benzoquinones; D029742:Caenorhabditis elegans Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin