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Exploring molecular variation in Schistosoma japonicum in China.

Young ND, Chan KG, Korhonen PK, Min Chong T, Ee R, Mohandas N, Koehler AV, Lim YL, Hofmann A, Jex AR, Qian B, Chilton NB, Gobert GN, McManus DP, Tan P, Webster BL, Rollinson D, Gasser RB - Sci Rep (2015)

Bottom Line: The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host.Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale.Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

View Article: PubMed Central - PubMed

Affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria 3010, Australia.

ABSTRACT
Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

No MeSH data available.


Related in: MedlinePlus

Sequence variability in the extracellular 2 domain (EC2) of the Schistosoma japonicum tetraspanin 2 ortholog (Sj-TSP2) among seven distinct populations.(A) Nucleotide logos represent the frequency of base calls for each population in sites containing single nucleotide polymorphisms (SNPs). Amino acid logos representing the consensus sequence for all seven populations. SNPs leading to a similar (yellow star) or distinct (white star) change of the translated amino acid are indicated. Each amino acid logo is coloured according to its chemical characteristics; polar residues (G, S, T, Y & C) are green, neutral (Q & N) are purple, basic (K, R & H) are blue, acidic (D & E) are red and hydrophobic (A, V, L, I, P, W, F & M) are black. The extracellular 2 (EC2) domain is highlighted in grey. (B) Comparison of consensus Sj-TSP2-EC2 structures, modelled using the resolved protein structure of Sm-TSP2-EC2 (labelled green; RCSB accession number: 2M7Z) and highlighting structural changes (a & b) in the head region associated with the consensus amino acid sequence composition of each S. japonicum isolate. Proteins structures (S. japonicum) are coloured by percentage amino acid conservation among consensus protein translations.
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f3: Sequence variability in the extracellular 2 domain (EC2) of the Schistosoma japonicum tetraspanin 2 ortholog (Sj-TSP2) among seven distinct populations.(A) Nucleotide logos represent the frequency of base calls for each population in sites containing single nucleotide polymorphisms (SNPs). Amino acid logos representing the consensus sequence for all seven populations. SNPs leading to a similar (yellow star) or distinct (white star) change of the translated amino acid are indicated. Each amino acid logo is coloured according to its chemical characteristics; polar residues (G, S, T, Y & C) are green, neutral (Q & N) are purple, basic (K, R & H) are blue, acidic (D & E) are red and hydrophobic (A, V, L, I, P, W, F & M) are black. The extracellular 2 (EC2) domain is highlighted in grey. (B) Comparison of consensus Sj-TSP2-EC2 structures, modelled using the resolved protein structure of Sm-TSP2-EC2 (labelled green; RCSB accession number: 2M7Z) and highlighting structural changes (a & b) in the head region associated with the consensus amino acid sequence composition of each S. japonicum isolate. Proteins structures (S. japonicum) are coloured by percentage amino acid conservation among consensus protein translations.

Mentions: Pairwise comparisons revealed nucleotide sequence variation of >2% in SCOs encoding structural proteins, molecules recognised to play important roles in regulating or modulating definitive host responses, and known immunogens (Fig. 2C and Supplementary Table 5). Variable structural proteins of cells included five cadherin/protocadherin-like molecules, dynein and actophorin and annexins (Supplementary Table 5). Variable proteins inferred to be involved in the pathogen-host interplay included a disulphide isomerase31, a thioredoxin32, a venom allergen-like (VAL20) protein33, heme-binding protein 134 and an extracellular superoxide dismutase35. Known immunogens included Sm14-like (fatty acid binding protein), Sm29-like36 and four tetraspanins (Fig. 2 and Supplementary Table 8). Sequence variability among some members of the tetraspanin protein family of S. japonicum was similar to a previous observation37 and was detected principally within Sj25 and the surface-exposed extracellular domain 2 (EC2) of the TSP2 ortholog (i.e. Sj-TSP2-EC2; Fig. 3, Supplementary Fig. 3 and Supplementary Table 8)37. Sj-TSP2-EC2 is encoded by a single SCO, and displays considerable nucleotide sequence variation (93.8–98.4%, respectively) within S. japonicum (Fig. 3A and Supplementary Table 8). A comparison of Sj-TSP2-EC2 domains, modelled using the resolved tertiary structure template of Sm-TSP2-EC238 (coverage: 96%; root-mean-square deviations between backbone atomic positions: ~2.4 Å), revealed “stem” regions that mediate contact with the plasma membrane38 and are structurally conserved between S. mansoni and all seven S. japonicum isolates (Fig. 3B). The “head region” of Sj-TSP2 is stabilised by two strictly conserved disulphide bridges38. However, mostly the surface-exposed amino acid residues in the head region are variable (Fig. 3Bb) in this TSP2 moiety between S. japonicum populations and between schistosome species. Compared with Sm-TSP2, the Sj-TSP2 EC2 domain lacks four residues, leading to a loss of the exposed hydrophobic patch in the head region38 (Fig. 3Bb). Other notable differences between S. japonicum populations include variation in features that likely affect protein-protein interactions, such as the change of surface electrostatics (K28T, D35S and K57N) and alterations that increase flexibility and thus allow for structural changes (P52R). In addition to variation in Sj-TSP2 was nucleotide sequence variability in tetraspanin-enriched-microdomain (TEM)38-associated proteins, including calpain (98.0–98.9%), annexin (97.4–100%) and an Sm29-like molecule (91.8–93.6%) (Supplementary Table 8). Importantly, variation in the Sm29-like protein was observed downstream of the N-terminal signal peptide and upstream of the C-terminal hydrophobic transmembrane domain (Supplementary Fig. 3), which has been used to assess immunoprotection in animals against S. mansoni infection39. Interestingly, there was a positive correlation (0.794) in sequence similarity between the Sj-TSP2 and the Sm29-like proteins within individual S. japonicum populations, suggesting that the evolution of these TEM-associated proteins might be linked.


Exploring molecular variation in Schistosoma japonicum in China.

Young ND, Chan KG, Korhonen PK, Min Chong T, Ee R, Mohandas N, Koehler AV, Lim YL, Hofmann A, Jex AR, Qian B, Chilton NB, Gobert GN, McManus DP, Tan P, Webster BL, Rollinson D, Gasser RB - Sci Rep (2015)

Sequence variability in the extracellular 2 domain (EC2) of the Schistosoma japonicum tetraspanin 2 ortholog (Sj-TSP2) among seven distinct populations.(A) Nucleotide logos represent the frequency of base calls for each population in sites containing single nucleotide polymorphisms (SNPs). Amino acid logos representing the consensus sequence for all seven populations. SNPs leading to a similar (yellow star) or distinct (white star) change of the translated amino acid are indicated. Each amino acid logo is coloured according to its chemical characteristics; polar residues (G, S, T, Y & C) are green, neutral (Q & N) are purple, basic (K, R & H) are blue, acidic (D & E) are red and hydrophobic (A, V, L, I, P, W, F & M) are black. The extracellular 2 (EC2) domain is highlighted in grey. (B) Comparison of consensus Sj-TSP2-EC2 structures, modelled using the resolved protein structure of Sm-TSP2-EC2 (labelled green; RCSB accession number: 2M7Z) and highlighting structural changes (a & b) in the head region associated with the consensus amino acid sequence composition of each S. japonicum isolate. Proteins structures (S. japonicum) are coloured by percentage amino acid conservation among consensus protein translations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664899&req=5

f3: Sequence variability in the extracellular 2 domain (EC2) of the Schistosoma japonicum tetraspanin 2 ortholog (Sj-TSP2) among seven distinct populations.(A) Nucleotide logos represent the frequency of base calls for each population in sites containing single nucleotide polymorphisms (SNPs). Amino acid logos representing the consensus sequence for all seven populations. SNPs leading to a similar (yellow star) or distinct (white star) change of the translated amino acid are indicated. Each amino acid logo is coloured according to its chemical characteristics; polar residues (G, S, T, Y & C) are green, neutral (Q & N) are purple, basic (K, R & H) are blue, acidic (D & E) are red and hydrophobic (A, V, L, I, P, W, F & M) are black. The extracellular 2 (EC2) domain is highlighted in grey. (B) Comparison of consensus Sj-TSP2-EC2 structures, modelled using the resolved protein structure of Sm-TSP2-EC2 (labelled green; RCSB accession number: 2M7Z) and highlighting structural changes (a & b) in the head region associated with the consensus amino acid sequence composition of each S. japonicum isolate. Proteins structures (S. japonicum) are coloured by percentage amino acid conservation among consensus protein translations.
Mentions: Pairwise comparisons revealed nucleotide sequence variation of >2% in SCOs encoding structural proteins, molecules recognised to play important roles in regulating or modulating definitive host responses, and known immunogens (Fig. 2C and Supplementary Table 5). Variable structural proteins of cells included five cadherin/protocadherin-like molecules, dynein and actophorin and annexins (Supplementary Table 5). Variable proteins inferred to be involved in the pathogen-host interplay included a disulphide isomerase31, a thioredoxin32, a venom allergen-like (VAL20) protein33, heme-binding protein 134 and an extracellular superoxide dismutase35. Known immunogens included Sm14-like (fatty acid binding protein), Sm29-like36 and four tetraspanins (Fig. 2 and Supplementary Table 8). Sequence variability among some members of the tetraspanin protein family of S. japonicum was similar to a previous observation37 and was detected principally within Sj25 and the surface-exposed extracellular domain 2 (EC2) of the TSP2 ortholog (i.e. Sj-TSP2-EC2; Fig. 3, Supplementary Fig. 3 and Supplementary Table 8)37. Sj-TSP2-EC2 is encoded by a single SCO, and displays considerable nucleotide sequence variation (93.8–98.4%, respectively) within S. japonicum (Fig. 3A and Supplementary Table 8). A comparison of Sj-TSP2-EC2 domains, modelled using the resolved tertiary structure template of Sm-TSP2-EC238 (coverage: 96%; root-mean-square deviations between backbone atomic positions: ~2.4 Å), revealed “stem” regions that mediate contact with the plasma membrane38 and are structurally conserved between S. mansoni and all seven S. japonicum isolates (Fig. 3B). The “head region” of Sj-TSP2 is stabilised by two strictly conserved disulphide bridges38. However, mostly the surface-exposed amino acid residues in the head region are variable (Fig. 3Bb) in this TSP2 moiety between S. japonicum populations and between schistosome species. Compared with Sm-TSP2, the Sj-TSP2 EC2 domain lacks four residues, leading to a loss of the exposed hydrophobic patch in the head region38 (Fig. 3Bb). Other notable differences between S. japonicum populations include variation in features that likely affect protein-protein interactions, such as the change of surface electrostatics (K28T, D35S and K57N) and alterations that increase flexibility and thus allow for structural changes (P52R). In addition to variation in Sj-TSP2 was nucleotide sequence variability in tetraspanin-enriched-microdomain (TEM)38-associated proteins, including calpain (98.0–98.9%), annexin (97.4–100%) and an Sm29-like molecule (91.8–93.6%) (Supplementary Table 8). Importantly, variation in the Sm29-like protein was observed downstream of the N-terminal signal peptide and upstream of the C-terminal hydrophobic transmembrane domain (Supplementary Fig. 3), which has been used to assess immunoprotection in animals against S. mansoni infection39. Interestingly, there was a positive correlation (0.794) in sequence similarity between the Sj-TSP2 and the Sm29-like proteins within individual S. japonicum populations, suggesting that the evolution of these TEM-associated proteins might be linked.

Bottom Line: The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host.Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale.Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

View Article: PubMed Central - PubMed

Affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria 3010, Australia.

ABSTRACT
Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

No MeSH data available.


Related in: MedlinePlus