The complex evolution of the metazoan HSP70 gene family

Abstract

The metazoan 70-kDa heat shock protein (HSP70) family contains several members localized in different subcellular compartments. The cytosolic members have been classified into inducible HSP70s and constitutive heat shock cognates (HSC70s), but their distinction and evolutionary relationship remain unclear because of occasional reports of “constitutive HSP70s” and the lack of cross-phylum comparisons. Here we provide novel insights into the evolution of these important molecular chaperones. Phylogenetic analyses of 125 full-length HSP70s from a broad range of phyla revealed an ancient duplication that gave rise to two lineages from which all metazoan cytosolic HSP70s descend. One lineage (A) contains a relatively small number of genes from many invertebrate phyla, none of which have been shown to be constitutively expressed (i.e., either inducible or unknown). The other lineage (B) included both inducible and constitutive genes from diverse phyla. Species-specific duplications are present in both lineages, and Lineage B contains well-supported phylum-specific clades for Platyhelminthes, Rotifera, Nematoda, Porifera/Cnidaria, and Chordata. Some genes in Lineage B have likely independently acquired inducibility, which may explain the sporadic distribution of “HSP70” or “HSC70” in previous phylogenetic analyses. Consistent with the diversification history within each group, inducible members show lower purifying selection pressure compared to constitutive members. These results illustrate the evolutionary history of the HSP70 family, encouraging us to propose a new nomenclature: “HSP70 + subcellular localization + linage + copy number in the organism + inducible or constitutive, if known.” e.g., HSP70cA1i for cytosolic Lineage A, copy 1, inducible.

Genome-Wide Analyses of Heat Shock Protein Superfamily Provide New Insights on Adaptation to Sulfide-Rich Environments in Urechis unicinctus (Annelida, Echiura)

“…The phylogenetic trees were constructed using the neighbor-joining method by MEGA 11.0 software ( , accessed on 7 February 2022) with bootstrap values from 1000 replicates indicated at each node with the following parameters: p -distance and pairwise deletion. Nomenclature of all HSP genes was completed based on the amino acid sequence similarities and phylogenetic analysis, and the HSP70s were renamed according to the new nomenclature which was proposed by Yu et al [ 69 ].…”

Diving into the Evolutionary History of HSC70-Linked Selective Autophagy Pathways: Endosomal Microautophagy and Chaperone-Mediated Autophagy

“…They have further been classified into either inducible HSP70s or constitutively expressed HSC70s, but until recently, their evolutionary relationship remained elusive, mainly due to the lack of cross-phylum comparisons. However, a recent in-depth phylogenetic study reviewing 125 complete HSP70/HSC70s genes from a wide range of species across different phyla has clarified the complex evolution of this gene family [ 32 ]. According to this study, HSP70 family members associate with mitochondria and the endoplasmic reticulum form two monophyletic groups ( Figure 3 ).…”

“…Interestingly, an inter-clade comparison of the synonymous and nonsynonymous substitution rates revealed that all HSP70/HSC70 family members are under strong purifying selection [ 32 ]. The presence of such a purifying selection was already reported for mammalian [ 33 ], nematode [ 34 ], molluscan [ 35 ], and protist [ 36 ] HSP70/HSC70 genes.…”

“… Proposed tree topology of HSP70/HSC70 family members in metazoans (adapted from Yu et al [ 32 ]). Red and green circles show the nodes that give birth to Lineage A of invertebrate HSP70s (clade 1) and Lineage B of both vertebrate and invertebrate HSP70s and all HSC70 genes, respectively.…”

The Effects of Heat Shock Protein 70 Addition in the Culture Medium on the Development and Quality of In Vitro Produced Heat Shocked Bovine Embryos

“…In vertebrates, there are two main forms of HSP70s: several members exhibit constitutive expression patterns, while others are induced by various stresses that disrupt proper protein folding and they are regulated by HSF1. The evolutionary histories of HSP70s, and especially of the inducible forms, are quite complex with events of convergent evolution and gene duplication among others; hence, a new nomenclature for their classification has been proposed [ 23 ], Yu et al, 2021. The HSPs are closely associated with the cellular response to a variety of stressors, and they are not merely linked to the heat stress, as it was initially believed [ 24 ].…”