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hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions.

Brocchieri L, Conway de Macario E, Macario AJ - BMC Evol. Biol. (2008)

Bottom Line: Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family.The human hsp70-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8.These functions may also be further defined by the observed differences in the N-terminal domain.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Florida, Department of Molecular Genetics and Microbiology and UF Genetics Institute, Gainesville, FL 32610, USA. lucianob@ufl.edu

ABSTRACT

Background: Hsp70 chaperones are required for key cellular processes and response to environmental changes and survival but they have not been fully characterized yet. The human hsp70-gene family has an unknown number of members (eleven counted over ten years ago); some have been described but the information is incomplete and inconsistent. A coherent body of knowledge encompassing all family components that would facilitate their study individually and as a group is lacking. Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family.

Results: We identified 47 hsp70 sequences, 17 genes and 30 pseudogenes. The genes distributed into seven evolutionarily distinct groups with distinguishable subgroups according to phylogenetic and other data, such as exon-intron and protein features. The N-terminal ATP-binding domain (ABD) was conserved at least partially in the majority of the proteins but the C-terminal substrate-binding domain (SBD) was not. Nine proteins were typical Hsp70s (65-80 kDa) with ABD and SBD, two were lighter lacking partly or totally the SBD, and six were heavier (>80 kDa) with divergent C-terminal domains. We also analyzed exon-intron features, transcriptional variants and protein structure and isoforms, and modality and patterns of expression in various tissues and developmental stages. Evolutionary analyses, including human hsp70 genes and pseudogenes, and other eukaryotic hsp70 genes, showed that six human genes encoding cytosolic Hsp70s and 27 pseudogenes originated from retro-transposition of HSPA8, a gene highly expressed in most tissues and developmental stages.

Conclusion: The human hsp70-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8. Human Hsp70 proteins are clustered into seven evolutionary Groups, with divergent C-terminal domains likely defining their distinctive functions. These functions may also be further defined by the observed differences in the N-terminal domain.

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Phylogenetic tree of eukaryotic Hsp70 protein 12. The tree includes the human HSPA12A and HSPA12B proteins and the homologs found in eighteen sequenced eukaryotic genomes. See legend for Figure 3 and text for methods and other details. Homologs of human HSPA12A and HSPA12B were found only in vertebrates. The evolutionary tree suggests that the human genes originated from a unique progenitor also appearing in fish possibly due to a duplication event that occurred in Tetrapoda before the divergence of Amphibia. Only one HSPA12 copy was found in reptiles and birds, suggesting gene loss (or extreme divergence) of one HSPA12 copy from this lineage.
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Figure 5: Phylogenetic tree of eukaryotic Hsp70 protein 12. The tree includes the human HSPA12A and HSPA12B proteins and the homologs found in eighteen sequenced eukaryotic genomes. See legend for Figure 3 and text for methods and other details. Homologs of human HSPA12A and HSPA12B were found only in vertebrates. The evolutionary tree suggests that the human genes originated from a unique progenitor also appearing in fish possibly due to a duplication event that occurred in Tetrapoda before the divergence of Amphibia. Only one HSPA12 copy was found in reptiles and birds, suggesting gene loss (or extreme divergence) of one HSPA12 copy from this lineage.

Mentions: We also searched for the genes encoding proteins like HSPA12A and HSPA12B in the sequenced genomes examined in Figure 3. We found homologs of these genes only in fish (Danio), Amphibian (Xenopus), Bird (chicken), and Mammal (human and mouse), a finding that together with their evolutionary relations shown in Figure 5, suggests that the various HSPA12 genes evolved at an early stage in the evolution of vertebrates (or that versions of the gene that diverged earlier do not conserve significant similarity to current human homologs). We found in Danio rerio (fish) three recently diverged copies of the gene (similarities 97–99%) that were quite diverged from the human and amphibian sequences (similarities in the range 25–32%). Chicken had only one copy, which was most similar to the human HSPA12B (92% similarity), whereas we found two copies of this gene in mammals and amphibians. The evolutionary tree of the gene suggests that the amphibian and mammalian copies resulted from a unique duplication event that occurred in the tetrapod lineage before the radiation of the amphibian and mammalian lineages. Within each of the one amphibian and two mammals examined, the two gene copies had similarities in the range 61–65%. Each paralog was quite conserved among the three groups, with similarities between mammals and amphibian of 82–83% for the HSPA12A paralog, and of 71–73% for the HSPA12B paralog, whereas between human and mouse similarities were 97% and 94%, respectively. The phylogenetic relations of the vertebrate lineages imply that one of the two copies of the gene has been lost from the chicken genome. Interestingly, we identified in the chicken genome a non-annotated sequence of 186 nt (positions 45,897,943–45,898,128 of chromosome 1) in the complementary strand, encoding a protein with 56.5% identity to a segment of the annotated chicken hspa12 gene. This short gene is possibly a remnant of HSPA12A.


hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions.

Brocchieri L, Conway de Macario E, Macario AJ - BMC Evol. Biol. (2008)

Phylogenetic tree of eukaryotic Hsp70 protein 12. The tree includes the human HSPA12A and HSPA12B proteins and the homologs found in eighteen sequenced eukaryotic genomes. See legend for Figure 3 and text for methods and other details. Homologs of human HSPA12A and HSPA12B were found only in vertebrates. The evolutionary tree suggests that the human genes originated from a unique progenitor also appearing in fish possibly due to a duplication event that occurred in Tetrapoda before the divergence of Amphibia. Only one HSPA12 copy was found in reptiles and birds, suggesting gene loss (or extreme divergence) of one HSPA12 copy from this lineage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266713&req=5

Figure 5: Phylogenetic tree of eukaryotic Hsp70 protein 12. The tree includes the human HSPA12A and HSPA12B proteins and the homologs found in eighteen sequenced eukaryotic genomes. See legend for Figure 3 and text for methods and other details. Homologs of human HSPA12A and HSPA12B were found only in vertebrates. The evolutionary tree suggests that the human genes originated from a unique progenitor also appearing in fish possibly due to a duplication event that occurred in Tetrapoda before the divergence of Amphibia. Only one HSPA12 copy was found in reptiles and birds, suggesting gene loss (or extreme divergence) of one HSPA12 copy from this lineage.
Mentions: We also searched for the genes encoding proteins like HSPA12A and HSPA12B in the sequenced genomes examined in Figure 3. We found homologs of these genes only in fish (Danio), Amphibian (Xenopus), Bird (chicken), and Mammal (human and mouse), a finding that together with their evolutionary relations shown in Figure 5, suggests that the various HSPA12 genes evolved at an early stage in the evolution of vertebrates (or that versions of the gene that diverged earlier do not conserve significant similarity to current human homologs). We found in Danio rerio (fish) three recently diverged copies of the gene (similarities 97–99%) that were quite diverged from the human and amphibian sequences (similarities in the range 25–32%). Chicken had only one copy, which was most similar to the human HSPA12B (92% similarity), whereas we found two copies of this gene in mammals and amphibians. The evolutionary tree of the gene suggests that the amphibian and mammalian copies resulted from a unique duplication event that occurred in the tetrapod lineage before the radiation of the amphibian and mammalian lineages. Within each of the one amphibian and two mammals examined, the two gene copies had similarities in the range 61–65%. Each paralog was quite conserved among the three groups, with similarities between mammals and amphibian of 82–83% for the HSPA12A paralog, and of 71–73% for the HSPA12B paralog, whereas between human and mouse similarities were 97% and 94%, respectively. The phylogenetic relations of the vertebrate lineages imply that one of the two copies of the gene has been lost from the chicken genome. Interestingly, we identified in the chicken genome a non-annotated sequence of 186 nt (positions 45,897,943–45,898,128 of chromosome 1) in the complementary strand, encoding a protein with 56.5% identity to a segment of the annotated chicken hspa12 gene. This short gene is possibly a remnant of HSPA12A.

Bottom Line: Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family.The human hsp70-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8.These functions may also be further defined by the observed differences in the N-terminal domain.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Florida, Department of Molecular Genetics and Microbiology and UF Genetics Institute, Gainesville, FL 32610, USA. lucianob@ufl.edu

ABSTRACT

Background: Hsp70 chaperones are required for key cellular processes and response to environmental changes and survival but they have not been fully characterized yet. The human hsp70-gene family has an unknown number of members (eleven counted over ten years ago); some have been described but the information is incomplete and inconsistent. A coherent body of knowledge encompassing all family components that would facilitate their study individually and as a group is lacking. Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family.

Results: We identified 47 hsp70 sequences, 17 genes and 30 pseudogenes. The genes distributed into seven evolutionarily distinct groups with distinguishable subgroups according to phylogenetic and other data, such as exon-intron and protein features. The N-terminal ATP-binding domain (ABD) was conserved at least partially in the majority of the proteins but the C-terminal substrate-binding domain (SBD) was not. Nine proteins were typical Hsp70s (65-80 kDa) with ABD and SBD, two were lighter lacking partly or totally the SBD, and six were heavier (>80 kDa) with divergent C-terminal domains. We also analyzed exon-intron features, transcriptional variants and protein structure and isoforms, and modality and patterns of expression in various tissues and developmental stages. Evolutionary analyses, including human hsp70 genes and pseudogenes, and other eukaryotic hsp70 genes, showed that six human genes encoding cytosolic Hsp70s and 27 pseudogenes originated from retro-transposition of HSPA8, a gene highly expressed in most tissues and developmental stages.

Conclusion: The human hsp70-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8. Human Hsp70 proteins are clustered into seven evolutionary Groups, with divergent C-terminal domains likely defining their distinctive functions. These functions may also be further defined by the observed differences in the N-terminal domain.

Show MeSH