The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families
Abstract
Hookworms infect over 400 million people, stunting and impoverishing them. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs). Genes downregulated during early infection included ion channels and G protein–coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.
Additional Information
© 2015 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. Received 12 January 2014; Accepted 05 February 2015; Published online 02 March 2015. We thank C.T. Brown, P.K. Korhonen, S. Kumar and J.E. Stajich for advice on bioinformatics, T.A. Aydin, J. Liu and A.H.K. Roeder for comments on the manuscript, L. Schaeffer and V. Kumar for genome and RNA sequencing, and C.T. Brown for use of the Michigan State University High-Performance Computing Center (supported by grant 2010-65205-20361 from the US Department of Agriculture and grant IOS-0923812 from the National Institute of Food and Agriculture and the National Science Foundation). Author Contributions: E.M.S., P.W.S. and R.V.A. conceived of and managed the project. Y.H. isolated genomic DNA and RNA from all infection stages of A. ceylanicum and converted RNA to cDNA for sequencing. M.M.M. maintained A. ceylanicum and golden hamster cultures through full life cycles and performed the photography for Figure 1. I.A. constructed large-insert paired-end and jumping Illumina libraries and supervised both genomic and RNA-seq Illumina sequencing. E.M.S. conducted all bioinformatics and biological analyses. Writing was primarily carried out by E.M.S. but with input from all authors.Attached Files
Published - ng.3237.pdf
Accepted Version - nihms681025.pdf
Supplemental Material - ng.3237-S1.pdf
Supplemental Material - ng.3237-S10.xlsx
Supplemental Material - ng.3237-S11.xlsx
Supplemental Material - ng.3237-S2.xlsx
Supplemental Material - ng.3237-S3.xlsx
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Supplemental Material - ng.3237-S6.xlsx
Supplemental Material - ng.3237-S7.xlsx
Supplemental Material - ng.3237-S8.xlsx
Supplemental Material - ng.3237-S9.xlsx
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Additional details
- PMCID
- PMC4617383
- Eprint ID
- 55529
- Resolver ID
- CaltechAUTHORS:20150305-080922455
- Department of Agriculture
- 2010-65205-20361
- NSF
- IOS-0923812
- Created
-
2015-03-05Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field