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Nature Genetics | Letter Open

日本語要約

Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade

Journal name:
Nature Genetics
Volume:
44,
Pages:
1051–1055
Year published:
DOI:
doi:10.1038/ng.2375
Received
Accepted
Published online

P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

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  1. Architecture of the P. cynomolgi genome and associated genome-wide variation data.
    Figure 1: Architecture of the P. cynomolgi genome and associated genome-wide variation data.

    Data are shown for each of the 14 P. cynomolgi chromosomes. The six concentric rings, from outermost to innermost, represent (i) the location of 5,049 P. cynomolgi genes, excluding those on small contigs (cyan lines); (ii) genome features, including 14 centromeres (thick black lines), 43 telomeric sequence repeats (short red lines), 43 tRNA genes (red lines), 10 rRNAs (dark blue lines) and several gene family members, including 53 cyir (dark green lines), 8 rbp (brown lines), 13 sera (serine-rich antigen; pink lines), 25 trag (tryptophan-rich antigen; purple lines), 12 msp3 (merozoite surface protein 3; light gray lines), 13 msp7 (merozoite surface protein 7; gray lines), 25 rad (silver lines), 8 etramp (orange lines), 16 Pf-fam-b (light blue lines) and 7 Pv-fam-d (light green lines); (iii) plot of dS/dN for 4,605 orthologs depicting genome-wide polymorphism within P. cynomolgi strains B and Berok (black line) and divergence between P. cynomolgi strains B and Berok and P. vivax Salvador I (red line); a track above the plot indicates P. cynomolgi genes under positive selection (red) and purifying selection (blue), and a track below the plot indicates P. cynomolgi–P. vivax orthologs under positive selection (red) and purifying selection (blue); (iv) heatmap indicating SNP density of 3 P. cynomolgi strains plotted per 10-kb windows: red, 0–83 SNPs per 10 kb (regions of lowest SNP density); blue, 84–166 SNPs per 10 kb; green, 167–250 SNPs per 10 kb; purple, 251–333 SNPs per 10 kb; orange, 334–416 SNPs per10 kb; yellow, 417–500 SNPs per10 kb (regions of highest SNP density); (v) log2 ratio plot of CNVs identified from a comparison of P. cynomolgi strains B and Berok; and (vi) map of 182 polymorphic intergenic microsatellites (MS, black dots). The figure was generated using Circos software (see URLs).

  2. Genome synteny between six species of Plasmodium parasite.
    Figure 2: Genome synteny between six species of Plasmodium parasite.

    Protein-coding genes of P. cynomolgi are shown aligned with those of five other Plasmodium genomes: two species belonging to the monkey malaria clade, P. vivax and P. knowlesi; two species of rodent malaria, P. berghei and P. chabaudi; and P. falciparum. Highly conserved protein-coding regions between the genomes are colored in order from red (5′ end of chromosome 1) to blue (3′ end of chromosome 14) with respect to genomic position of P. cynomolgi.

  3. Comparison of the genes of P. cynomolgi, P. vivax and P. knowlesi.
    Figure 3: Comparison of the genes of P. cynomolgi, P. vivax and P. knowlesi.

    The Venn ellipses represent the three genomes, with the total number of genes assigned to the chromosomes indicated under the species name. Cylinders depict orthologous and non-orthologous genes between the three genomes, with the number of genes in each indicated and represented graphically by cylinder relative width. In each cylinder, genes are divided into three categories whose thickness is represented by colored bands proportional to category percentage.

Accession codes

Primary accessions

DDBJ/GenBank/EMBL

NCBI Reference Sequence

Sequence Read Archive

Referenced accessions

NCBI Reference Sequence

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Author information

  1. These authors jointly directed this work.

    • Jane M Carlton &
    • Kazuyuki Tanabe

Affiliations

  1. Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

    • Shin-Ichiro Tachibana,
    • Hajime Honma &
    • Kazuyuki Tanabe

  2. Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, USA.

    • Steven A Sullivan,
    • Hyunjae R Kim,
    • Patrick L Sutton,
    • Rimma Shakhbatyan &
    • Jane M Carlton

  3. Laboratory of Tropical Medicine and Parasitology, Institute of International Education and Research, Dokkyo Medical University, Shimotsuga, Japan.

    • Satoru Kawai

  4. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

    • Shota Nakamura,
    • Naohisa Goto &
    • Teruo Yasunaga

  5. Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

    • Nobuko Arisue,
    • Nirianne M Q Palacpac,
    • Hajime Honma,
    • Masanori Yagi,
    • Takahiro Tougan,
    • Toshihiro Horii &
    • Kazuyuki Tanabe

  6. The Corporation for Production and Research of Laboratory Primates, Tsukuba, Japan.

    • Yuko Katakai

  7. Department of Protozoology, Institute of Tropical Medicine (NEKKEN) and Global COE (Centers of Excellence) Program, Nagasaki University, Nagasaki, Japan.

    • Osamu Kaneko

  8. Department of Molecular and Cellular Parasitology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

    • Toshihiro Mita

  9. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Kiyoshi Kita

  10. Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Japan.

    • Yasuhiro Yasutomi

  11. Center for Global Health, Centers for Disease Control and Prevention, Divison of Parasitic Diseases and Malaria, Atlanta, Georgia, USA.

    • John W Barnwell

  12. Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA.

    • Ananias A Escalante

  13. Present address: Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto, Japan.

    • Shin-Ichiro Tachibana

Contributions

K.T., J.M.C., A.A.E. and J.W.B. conceived and conducted the study. S.K., Y.K., Y.Y., S.-I.T. and J.W.B. provided P. cynomolgi material. S.N., N.G., T.Y. and H.R.K. constructed a computing system for data processing, and S.-I.T., H.H., P.L.S., S.A.S. and H.R.K. performed scaffolding of contigs and manual annotation of the predicted genes. S.N. performed sequence correction of supercontigs and gene prediction. S.-I.T., S.N., N.G., N.A., M.Y., O.K., K.T., H.R.K., R.S., S.A.S. and J.M.C. analyzed data. S.-I.T., N.M.Q.P., T.T., T.M., K.K., J.M.C., T.H., A.A.E., J.W.B. and K.T. wrote the manuscript.

Competing financial interests

The authors declare no competing financial interests.

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Supplementary information

PDF files

  1. Supplementary Text and Figures (6M)

    Supplementary Tables 1, 2, 4, 6, 8 , 9, 13 and 14, Supplementary Figures 1–5 and Supplementary Note

Excel files

  1. Supplementary Table 3 (2M)

    List of orthologs between the genomes of P. cynomolgi, P. vivax and P. knowlesi

  2. Supplementary Table 5 (119K)

    List of multigene families in P. cynomolgi, P. vivax and P. knowlesi

  3. Supplementary Table 7 (164K)

    List of P. cynomolgi cyir genes, P. vivax vir genes, P. knowlesi kir genes, and P. knowlesi SICAvar genes and their homologs in P. cynomolgi, P. vivax and P. knowlesi

  4. Supplementary Table 10 (74K)

    List of polymorphic microsatellite loci identified between P. cynomolgi strains B and Berok.

  5. Supplementary Table 11 (356K)

    Ds-Dn within 4,605 orthologs of P. cynomolgi strains B and Berok.

  6. Supplementary Table 12 (385K)

    Ds-Dn between 4,605 orthologs of P. cynomolgi strains B and Berok, and P. vivax Salvador I.

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