Research

Our main research areas are (1) Evolutionary innovation, (2) Biology of Symbionts & Parasites, and (3) Development of Nasonia as a Model Insect System

  1. Evolutionary Innovation: How do New Genes and Gene Functions Evolve? How do genomes evolve? Where do new genes and gene functions come from? We are investigating this question in two ways, briefly described below with some relevant references.

(a) Bacterial to Invertebrate Lateral Gene Transfers (LGTs) – Although transfers of bacterial genes into eukaryotic genomes was originally believed to be rare on non-existent, we now know this to be a relatively common mechanism of new gene acquisition in insects. How do LGTs evolve subsequent to transfer into vertebrate genomes. We are investigating LGTs in invertebrate using computational methods with follow-up analyses on interesting examples.

  1. Dunning Hotopp, J., M..E. Clark, P. Fischer, J. Foster, D. Oliveira, M.C.M. Torres, J. Giebel, S. Wang, R. Nene, J. Shepard, N. Ishmael, N. Kumar, E. Ghedin, J. Tomkins, S. Richards, D. Spiro, B. Slatko, H. Tettelin, and J.H. Werren. 2007. Widespread Lateral Gene Transfers from Intracellular Bacteria to Multicellular Eukaryotes. Science 317 (5845): 1753-1756).
  2. Wheeler, D, AJ Redding, and JH Werren. 2013. Characterization of an ancient lepidopteran lateral gene transfer. PLoS One 8: 1-9. e5926210.1371/journal.pone.0059262. PMID: 23533610.
  3. Martinson, EO, VG Martinson, RE Edwards, Mrinalini, and JH Werren. 2015 Laterally transferred gene recruited as a venom in parasitoid wasps. Mol. Biol. Evolution doi: 10.1093/molbev/msv348. PMC5013869.
  4. Benoit, JB, ZN Adelman, …..JH Werren, SR. Palli, C Schal, S Richards. 2016. Unique features of a global human ectoparasite identified through sequencing of the bed bug genome. 2016. Nature Communications 7: doi:10.1038/ncomms10165.
  5. Poynton,HC, S Hasenbein, JB Benoit, MS Sepulveda, MF. Poelchau, …, JH Werren, …, RA. Gibbs, S Richards. 2018. The Toxicogenome of Hyalella azteca: a model for sediment ecotoxicology and evolutionary toxicology.  Environmental Science and Technology.  DOI: 10.1021/acs.est.8b00837

(b) New Gene Functions by Gene Cooption & Expression Evolution:  The classic model for new gene function evolution is gene duplication followed by new function evolution. However, using rapidly evolving systems such as venom evolution and sex-biased gene evolution, we are finding that single copy genes can be recruited to new gene functions by rapid cis-regulatory changes.  Our goal is to determine how these systems evolve rapidly with genes acquiring new function.

  1. Martinson, EO, M Mrinalini, YD Kelkar, C-H Chang, JH Werren. 2017. The evolution of venom by co-option of single copy genes. Current Biology 27:2007-2013 e8.

 

  1. Martinson, EO, D Wheeler, J Wright, Mrinalini, AL Siebert, & JH Werren 2014. Nasonia venom causes targeted gene expression changes in its fly host. Molecular Ecology 23:5918-5930.
  2. Siebert, AL, D Wheeler, and JH Werren. 2015. A new approach for investigating venom function applied to venom calreticulin in a parasitoid wasp.   Toxicon 107:304-316 (Special Issue of Genomic Approaches in Venom Research) doi:10.1016/j.toxicon.2015.08.012. PMC4674333.
  3. Rago A, Werren JH, Colbourne JK. Sex biased expression and co-expression networks in development, using the hymenopteran Nasonia vitripennis. bioRxiv. 2019 Jan 1:540336.
  4. Martinson, E, AS Siebert, M He, Y Kelkar, L Doucette, & JH Werren. 2019. Evaluating the evolution and function of the dynamic Venom Y protein in ectoparasitoid wasps.  Insect Molecular Biology. doi.org/10.1111/imb.12565.
  5. Siebert, AS, LA Doucette, PJ Simpson-Haidaris, & JH Werren. 2019. Parasitoid wasp venom elevates sorbitol and alters expression of metabolic genes in human kidney cells. Accepted: Toxicon.
  6. Biology of Symbionts & Parasites: Parasitism and Mutualism pervades all levels of life, from genomes to ecosystems. Our laboratory group has a long history of investigating this topic across these biological levels, with particular focus on genomic parasites, symbiont-host interactions, mitochondrial-nuclear coevolution, and macroparasites (e.g. parasitoid wasps) and host biology.  Most recently we have developed an interest in the conceptual framework for microbiome-host biology.

(a) Genomic parasites (aka selfish genetic elements) & Genetic Conflict:  Our laboratory group has investigated the role of genomic parasites in evolution for several decades.  Below are some key references.

  1. Werren, J.H., U. Nur., and C.-I. Wu. 1988. Selfish genetic elements. Trends in Ecol.& Evolution  3:297-302.
  2. Hurst, G.D.D. and J.H. Werren. 2001. The role of selfish genetic elements in eukaryotic evolution. Nature Reviews 2:597-606.
  3. Werren, J.H. 2011. Selfish Genetic Elements, Genetic Conflict, and Evolutionary Innovation. Proc. Natl. Acad. Sci.  108:10863-10870.  PMID:2169039.

(b) Symbiosis & Heritable microorganisms: Some microbes are inherited during the reproduction of their hosts, and these have evolved various mechanisms to manipulate host reproduction in ways advantageous to the microbe. In this area, we have focused primarily on microorganisms that induce alterations of reproduction in the host (i.e. reproductive parasitism).  In particular, our laboratory has played an important role in revealing fascinating aspects of the biology of Wolbachia, from their basic ecology to roles in shaping host evolution.

  1. Werren, J.H. 1997. Biology of Wolbachia . Ann. Rev. Entom.   42:587 – 609.
  2. Bordenstein, S.R., F.P. O’Hara and J.H. Werren. 2001. Wolbachia-induced bidirectional incompatibility precedes other hybrid incompatibilities in Nasonia .  Nature 409:707-710.
  3. Werren, J.H., L. Baldo, and M.E. Clark. 2008 Wolbachia: Master Manipulators of Invertebrate Biology. Nature Reviews Microbiology 6:741-751.
  4. Newton, I, MC Clark, et al….and JH Werren. 2016. Genome Biology & Evolution. Comparative genomics of two closely related Wolbachia with different reproductive effects on hosts.  Genome Biology & Evolution. doi: 10.1093/gbe/evw096.
  5. Douglas, AE and JH Werren 2016. Holes in the Hologenome: Why host-microbial symbioses are not holobionts. mLife 7(2): e0299-15. doi: 10.1128/mBio.02099-15
  6. Wang X, X Xiong, W Cao, C Zhang, JH Werren3, and X Wang. 2018. Genome assembly of the A-group Wolbachia in Nasonia oneida and phylogenomic analysis of Wolbachia strains revealed genome evolution and lateral gene transfer. BioRxiv: doi:https://doi.org/10.1101/508408
  7. Lindsey, Amelia, YD Kelkar, X Wu, D Sun, EO Martinson, Z Yan, PF Rugman-Jones, DST Hughes, SC Murali, J Qu, S Dugan, SL Lee, H Chao, H Dinh, Y Han, HV Doddapaneni, KC Worley, DM Muzny, G Ye, RA Gibbs, S Richards, SV Yi, R, and JH Werren. 2018. Comparative genomics of the miniature wasp and pest control agent Trichogramma pretiosum.   BMC Biology 16 (1), 54

(c) Mitochondrial- nuclear interactions:  Mitochondria are derived from an ancient symbiosis, and retain their own (albeit streamlined) genome. This creates conditions for genetic conflict between nuclear and mitochondrial genes. In addition, the nuclear-encoded and mitochondrial-encoded proteins must work together to produce vital mitochondrial functions, such as oxidative phosphorylation. Thus, nuclear-encoded and mitochondrial-encoded components are expected to coevolve. We have investigated how cytonuclear evolution contributes to reproductive incompatibilities between species, and more recently how evolutionary rate correlations can be used to uncover novel interactions between nuclear-encoded and mitochondrial encoded proteins.

  1. Breeuwer, J.A.J. and J.H. Werren. 1995. Hybrid breakdown between two haplodiploid species: The role of nuclear and cytoplasmic genes. Evolution  49:705-717.
  2. Yan, Z, G. Ye and JH Werren. 2019. Evolutionary rate correlation between mitochondria and mitochondria-associated nuclear-encoded proteins in insects. Molecular Biology & Evolution Accepted (Minor Revision).
  3. Telschow, A, J. Gadau, JH Werren, and Y Kobayashi. 2019. Genetic incompatibilities between mitochondria and nuclear genes: effect on gene flow and speciation. Frontiers in Genetics 10: doi: 10.3389/fgene.2019.00062
  4. Havird, JC, ES Forstyth, AM Williams, JH Werren, DK Dowling and DB Sloan. 2019. Mitonuclear conflict: When good genomes go bad. Accepted:  Current Biology.
  5. Developing the Parasitoid Nasonia (& Relatives) as a Model Insect System: Nasonia (aka the Jewel Wasp) is an emerging model system for studies of genetics, genomics, development, and behavior. Nasonia is a small parasitoid insect that is emerging as an outstanding model for genetics, development, and parasitoid and hymenopteran biology. Advantages of the system are ease of laboratory rearing, a short generation time, closely related inter-fertile species, genetic and genomic resources, and haploid males derived from unfertilized eggs, the system has quickly advanced as a new model. Our research activities include development of genomic and genetic resources for Nasonia and its relatives, studies of development, behavior and speciation using the complex of closely related species, mechanisms of gene regulation, and evolution of parasitoid-host interactions including rapid evolution of the venom protein repertoire of parasitoids.  The system is also particularly useful for high school and college biology instruction, especially in small college settings, because of ease and cost their maintenance, and we promote this through education outreach.
  6. Werren, J.H., Richards, S., Desjardins, C.A., Niehuis, O., Gadau, J., Colbourne, J.K., et al. 2010. Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.   Science 327:343-348.
  7. Werren, J.H. and D. Loehlin. 2009. The Parasitoid Wasp Nasonia: An Emerging Model System With Haploid Male Genetics.  Cold Spring Harbor Protocols doi:10.1101/pdb.emo134. PMID:20147035.
  8. Loehlin, D., D. Oliveira, R. Edwards, J.D. Giebel, M. Clark, M.V. Cattani, L. van de Zande, E. Verhulst, L.W. Beukeboom, M. Munoz-Torres, and J.H. Werren. 2010. Non-coding Changes Cause Sex-specific Wing Size Differences Between Closely Related Species of Nasonia . PLOS Genetics 6(1):e1000821; doi:10.1371/journal.pgen.1000821.
  9. Loehlin, D.W. and J.H. Werren. 2012. Evolution of shape by multiple regulatory changes to a growth gene. Science  335:943-947.  DOI: 10.1126/science.1215193. PMID:21792226.
  10. Sackton, TB, JH Werren & AG Clark. 2014. Characterizing the infection-induced transcriptome of Nasonia vitripennis reveals a preponderance of taxonomically-restricted immune genes. PLoS One 8(12): e83984.  DOI: 10.1371/journal.pone.0083984.
  11. Werren, JH, LB Cohen, J Gadau, R Ponce, & JA Lynch. 2015. Dissection of the complex genetic basis of craniofacial anomalies using haploid genetics and interspecies hybrids in Nasonia wasps. Developmental Biology doi:10.1016/j.ydbio.2015.12.022. PMID: 26721604 PMC4914427.
  12. Rago, A, D Gilbert, J Choi, T Saxton, X. Wang, Y Kelkar, JH Werren, and JK Colbourne. 2016. OGS2: Genome Re-annotation of the Jewel Wasp Nasonia vitripennis. BMC Genomics 17:678. DOI: 10.1186/s12864-016-2886-9.
  13. Wang, X., D. Wheeler, A. Avery, A. Rago, J-H Choi, J.K. Colbourne, A.G. Clark, and J.H. Werren. 2013. Function and Evolution of DNA Methylation in Nasonia vitripennis. PLoS Genetics 9(10): e1003872. doi:10.1371/journal.pgen.1003872
  14. Lindsey, Amelia, YD Kelkar, X Wu, D Sun, EO Martinson, Z Yan, PF Rugman-Jones, DST Hughes, SC Murali, J Qu, S Dugan, SL Lee, H Chao, H Dinh, Y Han, HV Doddapaneni, KC Worley, DM Muzny, G Ye, RA Gibbs, S Richards, SV Yi, R, and JH Werren. 2018. Comparative genomics of the miniature wasp and pest control agent Trichogramma pretiosum.   BMC Biology 16 (1), 54