title: Species- and Strain-Specific Adaptation of the HSP70 Super Family in Pathogenic Trypanosomatids.
abstract: All eukaryotic genomes encode multiple members of the heat shock protein 70 (HSP70) family, which evolved distinctive structural and functional features in response to specific environmental constraints. Phylogenetic analysis of this protein family thus can inform on genetic and molecular mechanisms that drive species-specific environmental adaptation. Here we use the eukaryotic pathogen Leishmania spp. as a model system to investigate the evolution of the HSP70 protein family in an early-branching eukaryote that is prone to gene amplification and adapts to cytotoxic host environments by stress-induced and chaperone-dependent stage differentiation. Combining phylogenetic and comparative analyses of trypanosomatid genomes, draft genome of Paratrypanosoma and recently published genome sequences of 204 L. donovani field isolates, we gained unique insight into the evolutionary dynamics of the Leishmania HSP70 protein family. We provide evidence for (i) significant evolutionary expansion of this protein family in Leishmania through gene amplification and functional specialization of highly conserved canonical HSP70 members, (ii) evolution of trypanosomatid-specific, non-canonical family members that likely gained ATPase-independent functions, and (iii) loss of one atypical HSP70 member in the Trypanosoma genus. Finally, we reveal considerable copy number variation of canonical cytoplasmic HSP70 in highly related L. donovani field isolates, thus identifying this locus as a potential hot spot of environment-genotype interaction. Our data draw a complex picture of the genetic history of HSP70 in trypanosomatids that is driven by the remarkable plasticity of the Leishmania genome to undergo massive intra-chromosomal gene amplification to compensate for the absence of regulated transcriptional control in these parasites.
authors.affiliation: Unité de Parasitologie moléculaire et Signalisation, Department of Parasites and Insect Vectors, Institut Pasteur and INSERM U1201, Paris, France.
authors.forename: Sima
authors.initials: S
authors.lastname: Drini
authors.affiliation: Institut Pasteur - Hub Bioinformatique et Biostatistique - C3BI, Department of Genomes & Genetics, USR 3756 IP CNRS - Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Criscuolo
authors.affiliation: Institut Pasteur - Hub Bioinformatique et Biostatistique - C3BI, Department of Genomes & Genetics, USR 3756 IP CNRS - Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lechat
authors.affiliation: Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium.
authors.forename: Hideo
authors.initials: H
authors.lastname: Imamura
authors.affiliation: Institute of Parasitology, Biology Centre, Czech Academy of Sciences, and Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Skalický
authors.affiliation: Unité de Parasitologie moléculaire et Signalisation, Department of Parasites and Insect Vectors, Institut Pasteur and INSERM U1201, Paris, France.
authors.forename: Najma
authors.initials: N
authors.lastname: Rachidi
authors.affiliation: Institute of Parasitology, Biology Centre, Czech Academy of Sciences, and Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic Canadian Institute for Advanced Research, Toronto, Canada.
authors.forename: Julius
authors.initials: J
authors.lastname: Lukeš
authors.affiliation: Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.affiliation: Unité de Parasitologie moléculaire et Signalisation, Department of Parasites and Insect Vectors, Institut Pasteur and INSERM U1201, Paris, France gerald.spaeth@pasteur.fr.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Späth
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations / Q000235:genetics; D019143:Evolution, Molecular; D005784:Gene Amplification / Q000235:genetics; D016678:Genome; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007891:Leishmania / Q000235:genetics* / Q000472:pathogenicity; D007896:Leishmaniasis / Q000235:genetics* / Q000469:parasitology; D010802:Phylogeny; D013045:Species Specificity
chemical_list: D018840:HSP70 Heat-Shock Proteins
keywords: HSP70; Leishmania; copy number variation; evolution; gene loss; heat shock protein; phylogeny; synteny