. 2016 Feb 2:7:10165.

doi: 10.1038/ncomms10165.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

Joshua B Benoit¹, Zach N Adelman², Klaus Reinhardt³, Amanda Dolan⁴, Monica Poelchau⁵, Emily C Jennings¹, Elise M Szuter¹, Richard W Hagan¹, Hemant Gujar⁶, Jayendra Nath Shukla⁶, Fang Zhu^{6

7}, M Mohan⁸, David R Nelson⁹, Andrew J Rosendale¹, Christian Derst¹⁰, Valentina Resnik¹¹, Sebastian Wernig¹¹, Pamela Menegazzi¹², Christian Wegener¹², Nicolai Peschel¹², Jacob M Hendershot¹, Wolfgang Blenau¹⁰, Reinhard Predel¹⁰, Paul R Johnston¹³, Panagiotis Ioannidis¹⁴, Robert M Waterhouse^{14

15}, Ralf Nauen¹⁶, Corinna Schorn¹⁶, Mark-Christoph Ott¹⁶, Frank Maiwald¹⁶, J Spencer Johnston¹⁷, Ameya D Gondhalekar¹⁸, Michael E Scharf¹⁸, Brittany F Peterson¹⁸, Kapil R Raje¹⁸, Benjamin A Hottel¹⁹, David Armisén²⁰, Antonin Jean Johan Crumière²⁰, Peter Nagui Refki²⁰, Maria Emilia Santos²⁰, Essia Sghaier²⁰, Sèverine Viala²⁰, Abderrahman Khila²⁰, Seung-Joon Ahn²¹, Christopher Childers⁵, Chien-Yueh Lee^{5

22}, Han Lin^{5

22}, Daniel S T Hughes²³, Elizabeth J Duncan²⁴, Shwetha C Murali²³, Jiaxin Qu²³, Shannon Dugan²³, Sandra L Lee²³, Hsu Chao²³, Huyen Dinh²³, Yi Han²³, Harshavardhan Doddapaneni²³, Kim C Worley²³, Donna M Muzny²³, David Wheeler²⁵, Kristen A Panfilio²⁶, Iris M Vargas Jentzsch²⁶, Edward L Vargo¹⁷, Warren Booth²⁷, Markus Friedrich²⁸, Matthew T Weirauch²⁹, Michelle A E Anderson², Jeffery W Jones²⁸, Omprakash Mittapalli³⁰, Chaoyang Zhao³⁰, Jing-Jiang Zhou³¹, Jay D Evans³², Geoffrey M Attardo³³, Hugh M Robertson³⁴, Evgeny M Zdobnov¹⁴, Jose M C Ribeiro³⁵, Richard A Gibbs²³, John H Werren⁴, Subba R Palli⁶, Coby Schal³⁶, Stephen Richards²³

Affiliations

¹ Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio 45221, USA.
² Fralin Life Science Institute and Department of Entomology, Virginia Tech, Blacksburg, Virginia 24061, USA.
³ Department of Biology, Applied Zoology, Technische Universitaet Dresden, Dresden 01062, Germany.
⁴ Department of Biology, University of Rochester, Rochester, New York 14627, USA.
⁵ National Agricultural Library, Beltsville, Maryland 20705, USA.
⁶ Department of Entomology, University of Kentucky, Lexington, Kentucky 40546, USA.
⁷ Department of Entomology, Washington State University, Pullman, Washington 99164, USA.
⁸ ICAR-National Bureau of Agricultural Insect Resources, Indian Council of Agricultural Research, Bengaluru 560024, India.
⁹ Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA.
¹⁰ Cologne Biocenter and Zoological Institute, University of Cologne, Cologne 50674, Germany.
¹¹ Institut für Bienenkunde (Polytechnische Gesellschaft), Goethe University Frankfurt, Oberursel 61440, Germany.
¹² Department of Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, University of Würzburg, Würzburg 97074, Germany.
¹³ Department of Evolutionary Biology, Institute of Biology, Freie Universitaet, Berlin 14195, Germany.
¹⁴ Department of Genetic Medicine and Development and Swiss Institute of Bioinformatics, University of Geneva, Geneva 1211, Switzerland.
¹⁵ Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology and The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.
¹⁶ Pest Control Biology and Research Technologies, Bayer CropScience AG, Monheim 40789, Germany.
¹⁷ Department of Entomology, Texas A&M University, College Station, Texas 77843, USA.
¹⁸ Department of Entomology, Purdue University, West Lafayette, Indiana 47907, USA.
¹⁹ Department of Entomology and Nematology, University of Florida, Gainesville, Florida 32611, USA.
²⁰ Institue de Génomique Fonctionnelle de Lyon (IGFL), Ecole Normale Supérieure de Lyon, UMR5242-CNRS, Lyon 69007, France.
²¹ Department of Entomology, Max Planck Institute for Chemical Ecology, Jena 07745, Germany.
²² Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
²³ Human Genome Sequencing Center, Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
²⁴ Department of Biochemistry and Genetics Otago, University of Otago, Dunedin 9054, New Zealand.
²⁵ Institute of Fundamental Science, Massey University, Palmerston North 4442, New Zealand.
²⁶ Institute for Developmental Biology, University of Cologne, Cologne 50674, Germany.
²⁷ Department of Biological Sciences, University of Tulsa, Tulsa, Oklahoma 74104, USA.
²⁸ Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
²⁹ Center for Autoimmune Genomics and Etiology, Division of Biomedical Informatics, and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45229, USA.
³⁰ Department of Entomology, The Ohio State University, Wooster, Ohio 44691, USA.
³¹ Department of Biological Chemistry and Crop Protection, Rothamsted Research, BBSRC Harpenden, Herts AL5 2JQ, UK.
³² United States Department of Agriculture-Agricultural Research Service Bee Research Laboratory, Beltsville, Maryland 20705, USA.
³³ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut 06520, USA.
³⁴ Department of Entomology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
³⁵ Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, Bethesda, Maryland 20892, USA.
³⁶ Department of Entomology and W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.

PMID: 26836814
PMCID: PMC4740739
DOI: 10.1038/ncomms10165

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

Joshua B Benoit et al. Nat Commun. 2016.

. 2016 Feb 2:7:10165.

doi: 10.1038/ncomms10165.

Authors

Affiliations

¹ Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio 45221, USA.
² Fralin Life Science Institute and Department of Entomology, Virginia Tech, Blacksburg, Virginia 24061, USA.
³ Department of Biology, Applied Zoology, Technische Universitaet Dresden, Dresden 01062, Germany.
⁴ Department of Biology, University of Rochester, Rochester, New York 14627, USA.
⁵ National Agricultural Library, Beltsville, Maryland 20705, USA.
⁶ Department of Entomology, University of Kentucky, Lexington, Kentucky 40546, USA.
⁷ Department of Entomology, Washington State University, Pullman, Washington 99164, USA.
⁸ ICAR-National Bureau of Agricultural Insect Resources, Indian Council of Agricultural Research, Bengaluru 560024, India.
⁹ Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA.
¹⁰ Cologne Biocenter and Zoological Institute, University of Cologne, Cologne 50674, Germany.
¹¹ Institut für Bienenkunde (Polytechnische Gesellschaft), Goethe University Frankfurt, Oberursel 61440, Germany.
¹² Department of Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, University of Würzburg, Würzburg 97074, Germany.
¹³ Department of Evolutionary Biology, Institute of Biology, Freie Universitaet, Berlin 14195, Germany.
¹⁴ Department of Genetic Medicine and Development and Swiss Institute of Bioinformatics, University of Geneva, Geneva 1211, Switzerland.
¹⁵ Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology and The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.
¹⁶ Pest Control Biology and Research Technologies, Bayer CropScience AG, Monheim 40789, Germany.
¹⁷ Department of Entomology, Texas A&M University, College Station, Texas 77843, USA.
¹⁸ Department of Entomology, Purdue University, West Lafayette, Indiana 47907, USA.
¹⁹ Department of Entomology and Nematology, University of Florida, Gainesville, Florida 32611, USA.
²⁰ Institue de Génomique Fonctionnelle de Lyon (IGFL), Ecole Normale Supérieure de Lyon, UMR5242-CNRS, Lyon 69007, France.
²¹ Department of Entomology, Max Planck Institute for Chemical Ecology, Jena 07745, Germany.
²² Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
²³ Human Genome Sequencing Center, Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
²⁴ Department of Biochemistry and Genetics Otago, University of Otago, Dunedin 9054, New Zealand.
²⁵ Institute of Fundamental Science, Massey University, Palmerston North 4442, New Zealand.
²⁶ Institute for Developmental Biology, University of Cologne, Cologne 50674, Germany.
²⁷ Department of Biological Sciences, University of Tulsa, Tulsa, Oklahoma 74104, USA.
²⁸ Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
²⁹ Center for Autoimmune Genomics and Etiology, Division of Biomedical Informatics, and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45229, USA.
³⁰ Department of Entomology, The Ohio State University, Wooster, Ohio 44691, USA.
³¹ Department of Biological Chemistry and Crop Protection, Rothamsted Research, BBSRC Harpenden, Herts AL5 2JQ, UK.
³² United States Department of Agriculture-Agricultural Research Service Bee Research Laboratory, Beltsville, Maryland 20705, USA.
³³ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut 06520, USA.
³⁴ Department of Entomology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
³⁵ Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, Bethesda, Maryland 20892, USA.
³⁶ Department of Entomology and W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.

PMID: 26836814
PMCID: PMC4740739
DOI: 10.1038/ncomms10165

Abstract

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.

PubMed Disclaimer

Figures

**Figure 1. Phylogenetic placement and orthology comparison among *Cimex lectularius* and other arthropod species.**
The phylogenetic analysis places *C. lectularius* as a sister species to another hemipteran, *Acyrthosiphon pisum*. The phylogeny is built using RAxML and it is based on the 1,734 single-copy orthologues that are present in all eight species. All nodes in the phylogenetic tree have 100% bootstrap support, while the branch length unit is substitutions per site. There are 1,734 genes that are present as single copy in all eight species tested. Another 4,187 of the *C. lectularius* genes are found in varying copy number in the other seven species, while 2,433 are found in the majority of species (that is, in 5–7 species) and 2,153 genes are found in ≥2 species (that is, in 2–4 species). Moreover, 1,147 genes have an orthologue in an arthropod other than the selected seven species. Last, 2,285 genes are lineage specific and do not have an orthologue in any other arthropod species.

**Figure 2. Aspects related to host location and blood feeding identified based on the C. *lectularius* genome.**
(a) Genes associated with chemical reception among multiple insect species. *Zootermopsis nevadensis* (b) Genes associated with saliva function among multiple insect species. (c) Phylogeny of cathepsin D genes among multiple insect species. Sequences derived from *Cimex lectularius* (Cl) are denoted with red triangles and those derived from *Rhodnius prolixus* (Rp) are denoted with orange triangles. Other insect cathepsin D proteins represent those of *Triatoma infestans* (Ti), *Acyrthosiphon pisum* (Ap), *Anopheles gambiae* (Ag), *Drosophila melanogaster* (Dm), *Pediculus humanus corporis* (Ph), *Apis mellifera* (Am), *Nasonia vitripennis* (Nvi), *Tribolium castaneum* (Tc), *Callosobruchus maculatus* (Cm), *Sitophilus zeamais* (Sz), *Chrysomela tremula* (Ct), *Maconellicoccus hirsutus* (Mh), *Nematostella vectensis* (Nve), *Culex quinquefasciatus* (Cq) and *Aedes aegypti* (Aa).

**Figure 3. Summary of putative lateral gene transfers (LGTs) >100 bp in the *C. lectularius* assembly.**
(a) Number of candidate LGTs identified. (b) Length of candidate LGTs in bins spanning 10 bp.

**Figure 4. Synopsis of the contributions from the C. *lectularius* genome to understanding key biological processes.**
Red, general characteristics of bed bugs; black, key aspects identified and expanded by genome sequencing and manual curation.

See this image and copyright information in PMC

Cited by

Dynamics of Insect-Microbiome Interaction Influence Host and Microbial Symbiont.
Gupta A, Nair S. Gupta A, et al. Front Microbiol. 2020 Jun 26;11:1357. doi: 10.3389/fmicb.2020.01357. eCollection 2020. Front Microbiol. 2020. PMID: 32676060 Free PMC article. Review.
Repertoire-wide gene structure analyses: a case study comparing automatically predicted and manually annotated gene models.
Wilbrandt J, Misof B, Panfilio KA, Niehuis O. Wilbrandt J, et al. BMC Genomics. 2019 Oct 17;20(1):753. doi: 10.1186/s12864-019-6064-8. BMC Genomics. 2019. PMID: 31623555 Free PMC article.
Persistent Parental RNAi in the Beetle Tribolium castaneum Involves Maternal Transmission of Long Double-Stranded RNA.
Horn T, Narov KD, Panfilio KA. Horn T, et al. Adv Genet (Hoboken). 2022 Mar 20;3(3):2100064. doi: 10.1002/ggn2.202100064. eCollection 2022 Sep. Adv Genet (Hoboken). 2022. PMID: 36620196 Free PMC article.
Transcriptomic resources for Bagrada hilaris (Burmeister), a widespread invasive pest of Brassicales.
Sparks ME, Nelson DR, Harrison RL, Larson NR, Kuhar D, Haber AI, Heraghty SD, Rebholz Z, Tholl D, Grettenberger IM, Weber DC, Gundersen-Rindal DE. Sparks ME, et al. PLoS One. 2024 Dec 27;19(12):e0310186. doi: 10.1371/journal.pone.0310186. eCollection 2024. PLoS One. 2024. PMID: 39729495 Free PMC article.
The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species.
Papanicolaou A, Schetelig MF, Arensburger P, Atkinson PW, Benoit JB, Bourtzis K, Castañera P, Cavanaugh JP, Chao H, Childers C, Curril I, Dinh H, Doddapaneni H, Dolan A, Dugan S, Friedrich M, Gasperi G, Geib S, Georgakilas G, Gibbs RA, Giers SD, Gomulski LM, González-Guzmán M, Guillem-Amat A, Han Y, Hatzigeorgiou AG, Hernández-Crespo P, Hughes DS, Jones JW, Karagkouni D, Koskinioti P, Lee SL, Malacrida AR, Manni M, Mathiopoulos K, Meccariello A, Munoz-Torres M, Murali SC, Murphy TD, Muzny DM, Oberhofer G, Ortego F, Paraskevopoulou MD, Poelchau M, Qu J, Reczko M, Robertson HM, Rosendale AJ, Rosselot AE, Saccone G, Salvemini M, Savini G, Schreiner P, Scolari F, Siciliano P, Sim SB, Tsiamis G, Ureña E, Vlachos IS, Werren JH, Wimmer EA, Worley KC, Zacharopoulou A, Richards S, Handler AM. Papanicolaou A, et al. Genome Biol. 2016 Sep 22;17(1):192. doi: 10.1186/s13059-016-1049-2. Genome Biol. 2016. PMID: 27659211 Free PMC article.

See all "Cited by" articles

References

1. Panagiotakopulu E. & Buckland P. C. Cimex lectularius L., the common bed bug from Pharanic Egypt. Antiquity 73, 908–911 (1999).
1. Doggett S. L., Dwyer D. E., Penas P. F. & Russell R. C. Bed bugs: clinical relevance and control options. Clin. Microbiol. Rev. 25, 164–192 (2012). - PMC - PubMed
1. Potter M., Rosenberg B. & Henriksen M. Bugs without borders: defining the global bed bug resurgence. Pest World 18, 8–20 (2010).
1. Zhu F. et al. Bed bugs evolved unique adaptive strategy to resist pyrethroid insecticides. Sci. Rep. 3, 1456 (2013). - PMC - PubMed
1. Reinhardt K. & Siva-Jothy M. T. Biology of the bed bugs (Cimicidae). Annu. Rev. Entomol. 52, 351–374 (2007). - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

UL1 TR001427/TR/NCATS NIH HHS/United States

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

Affiliations

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous