The complex evolution of the HSP70 gene family

The 70-kDa heat shock protein (HSP70) family contains several isoforms localized in different subcellular compartments. The cytosolic isoforms have been classified into stress-inducible HSP70s and constitutive heat shock cognates (HSC70s), but occasional reports of "constitutive HSP70s" and the lack of cross-phylum comparisons have been a source of confusion in the evolution of the metazoan HSP70 family. Here we provide novel insights into the evolutionary history of this important molecular chaperone. We first cloned two HSP70 genes from the rotifer Brachionus plicatilis, an emerging model in evolutionary genetics, and confirmed their stress inducibility. Subsequent phylogenetic analyses of 100 full-length HSP70 family member genes revealed an ancient duplication that gave rise to two lineages from which all metazoan cytosolic HSP70s descend. One lineage contains a relatively small number of Lophotrochozoan and Ecdysozoan genes, none of which have been shown to be constitutively expressed. The second included both inducible and constitutive genes from diverse phyla. Species-specific duplications are present in both lineages, and in the second there are well-supported phylum-specific clades for Rotifera, Nematoda, and Chordata. Some genes in this lineage have likely independently acquired stress inducibility, which may explain the sporadic distribution of genes designated as "HSP70" or "HSC70" in previous analyses. Consistent with the history of diversification within each group, stress-inducible members of the second lineage show lower purifying selection pressure compared to constitutive members. These results illustrate the evolutionary history of the HSP70 family independent from their expression patterns, encouraging the development of new nomenclature based on evolutionary history.