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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 conservation and variation in single copy orthologs (SCOs) among seven distinct populations of Schistosoma japonicum.(A) Ranked SCOs, according to pairwise nucleotide sequence identities across coding domains. (B) Locally weighted linear regression (LOWESS) analysis of pairwise nucleotide identity, and amino acid identity and similarity among SCOs, ranked according to pairwise nucleotide sequence identities. Invariable SCOs, with >99.8% pairwise nucleotide identity among all populations, are indicated/boxed in black (left). Variable SCOs with one or more pairwise nucleotide identities ≤98% are indicated/boxed in red (right). Significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways and protein families as well as proteins involved in the pathogen-host interplay and other biological processes among (C) invariable and (D) variable SCOs are listed.
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f2: Sequence conservation and variation in single copy orthologs (SCOs) among seven distinct populations of Schistosoma japonicum.(A) Ranked SCOs, according to pairwise nucleotide sequence identities across coding domains. (B) Locally weighted linear regression (LOWESS) analysis of pairwise nucleotide identity, and amino acid identity and similarity among SCOs, ranked according to pairwise nucleotide sequence identities. Invariable SCOs, with >99.8% pairwise nucleotide identity among all populations, are indicated/boxed in black (left). Variable SCOs with one or more pairwise nucleotide identities ≤98% are indicated/boxed in red (right). Significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways and protein families as well as proteins involved in the pathogen-host interplay and other biological processes among (C) invariable and (D) variable SCOs are listed.

Mentions: We mapped the sequence reads derived from individual populations to a reference nuclear genomic sequence of S. japonicum (designated here as SjRef; Bioproject accession no. PRJEA34885)13. Overall, 82.6 to 88.0% of all reads mapped to this draft reference genome, with ~95% of these mapping as pairs (Supplementary Table 4). Excluding ambiguous positions (i.e. Ns in SjRef), 6,879,937 to 7,509,073 single nucleotide polymorphisms (SNPs) were recorded in individual populations (Table 2), of which 69% (n = 4,767,718 to 5,196,811), 26% (n = 1,784,457 to 1,948,205) and 1.6% (n = 107,446 to 121,775) were within intergenic, intronic and protein-encoding regions, respectively. For individual S. japonicum populations, 55,316 to 64,473 non-synonymous and 51,389 to 57,725 synonymous SNPs were identified in coding domains (Table 2). Employing published genomes, we identified 4,413 single-copy orthologs (SCOs) that were common to S. japonicum13, S. haematobium14 and S. mansoni30. Of the 4,413 single-copy orthologs (SCOs), 697,639 to 768,044 intronic, and 37,273 to 42,333 exonic SNPs were identified in protein-encoding gene regions, with 17,035 to 19,931 non-synonymous and 19,723 to 22,402 synonymous SNPs in individual S. japonicum populations (Table 3). For all SCOs, on average, 6.4 SNPs were detected in S. japonicum per kb of coding sequence (Table 3). The effect of nucleotide polymorphisms in SCOs on variation in the inferred proteins varied considerably; and, variation was reduced by an accumulation of synonymous mutations (recorded as amino acid identity) or mutations substituting amino acid residues with conserved chemical properties (recorded as amino acid similarity) (Fig. 2B and Supplementary Table 5).


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 conservation and variation in single copy orthologs (SCOs) among seven distinct populations of Schistosoma japonicum.(A) Ranked SCOs, according to pairwise nucleotide sequence identities across coding domains. (B) Locally weighted linear regression (LOWESS) analysis of pairwise nucleotide identity, and amino acid identity and similarity among SCOs, ranked according to pairwise nucleotide sequence identities. Invariable SCOs, with >99.8% pairwise nucleotide identity among all populations, are indicated/boxed in black (left). Variable SCOs with one or more pairwise nucleotide identities ≤98% are indicated/boxed in red (right). Significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways and protein families as well as proteins involved in the pathogen-host interplay and other biological processes among (C) invariable and (D) variable SCOs are listed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Sequence conservation and variation in single copy orthologs (SCOs) among seven distinct populations of Schistosoma japonicum.(A) Ranked SCOs, according to pairwise nucleotide sequence identities across coding domains. (B) Locally weighted linear regression (LOWESS) analysis of pairwise nucleotide identity, and amino acid identity and similarity among SCOs, ranked according to pairwise nucleotide sequence identities. Invariable SCOs, with >99.8% pairwise nucleotide identity among all populations, are indicated/boxed in black (left). Variable SCOs with one or more pairwise nucleotide identities ≤98% are indicated/boxed in red (right). Significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways and protein families as well as proteins involved in the pathogen-host interplay and other biological processes among (C) invariable and (D) variable SCOs are listed.
Mentions: We mapped the sequence reads derived from individual populations to a reference nuclear genomic sequence of S. japonicum (designated here as SjRef; Bioproject accession no. PRJEA34885)13. Overall, 82.6 to 88.0% of all reads mapped to this draft reference genome, with ~95% of these mapping as pairs (Supplementary Table 4). Excluding ambiguous positions (i.e. Ns in SjRef), 6,879,937 to 7,509,073 single nucleotide polymorphisms (SNPs) were recorded in individual populations (Table 2), of which 69% (n = 4,767,718 to 5,196,811), 26% (n = 1,784,457 to 1,948,205) and 1.6% (n = 107,446 to 121,775) were within intergenic, intronic and protein-encoding regions, respectively. For individual S. japonicum populations, 55,316 to 64,473 non-synonymous and 51,389 to 57,725 synonymous SNPs were identified in coding domains (Table 2). Employing published genomes, we identified 4,413 single-copy orthologs (SCOs) that were common to S. japonicum13, S. haematobium14 and S. mansoni30. Of the 4,413 single-copy orthologs (SCOs), 697,639 to 768,044 intronic, and 37,273 to 42,333 exonic SNPs were identified in protein-encoding gene regions, with 17,035 to 19,931 non-synonymous and 19,723 to 22,402 synonymous SNPs in individual S. japonicum populations (Table 3). For all SCOs, on average, 6.4 SNPs were detected in S. japonicum per kb of coding sequence (Table 3). The effect of nucleotide polymorphisms in SCOs on variation in the inferred proteins varied considerably; and, variation was reduced by an accumulation of synonymous mutations (recorded as amino acid identity) or mutations substituting amino acid residues with conserved chemical properties (recorded as amino acid similarity) (Fig. 2B and Supplementary Table 5).

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