Our areas of interest are evolutionary and functional genetics. We combine genetic, genomic, molecular, and population approaches to investigate basic questions in biology. There is an overall theme to our research – we are interested in interactions among biological entities. This includes genes within genomes, individuals within species, and interactions among species. Our current main research areas are listed below, along with some select references. Please click on the links for more information
A. Genome Evolution & the Origins of Innovation
How do genomes evolve? Where do new genes and evolutionary innovations come from? These remain central questions in Biology. Besides the classic model of new gene evolution through gene duplication and functional divergence, other mechanisms are receiving increasing attention as a source of evolutionary innovation. We are focusing on two, the roles of (a) lateral gene transfers from microbes to animals and (b) genetic conflict and selfish genetic elements (SGEs), as mechanisms in the evolution of new genes and novel functions. We also investigate other features of genome evolution, such as DNA methylation.
(1) Microbial-Animal Lateral Gene Transfers: Lateral gene transfer is known to be common among bacteria (e.g. antibiotic resistance encoded on plasmids), but was thought to be rare or non-existence between microbes and animals. In the past decade, this view has changed, including our finding that LGTs from the intracellular bacterium Wolbachia are common in invertebrate genomes (Dunning-Hotopp et al 2007). The major question remains, to what extent do these LGTs contribute to new gene functions in animals? We are systematically screening arthropod genomes and finding that LGTs of microbial origin which have evolved into functional genes are present in many arthropod genomes, and likely provide significant novel gene functions. This exciting work is ongoing, and a few references are below.
- 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).
- 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
- 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.
(2) Genetic Conflict & Parasitic (Selfish) DNA: Selfish (or parasitic) DNA generates conflict within genomes that can be a major source of evolutionary change and innovation. We have been working on parasitic DNA for many years, including studies of how such elements can cause evolution of sex determination and changes in genome organization. A few key references are below.
- Werren, J.H., U. Nur., and C.-I. Wu. 1988. Selfish genetic elements. Trends in Ecol.& Evolution 3:297-302.
- Hurst, G.D.D. and J.H. Werren. 2001. The role of selfish genetic elements in eukaryotic evolution. Nature Reviews 2:597-606.
- Werren, J.H. 2011. Selfish Genetic Elements, Genetic Conflict, and Evolutionary Innovation. Proc. Natl. Acad. Sci. 108:10863-10870. PMID:2169039.
(3) DNA Methylation in Insects: In insects, DNA methylation appears to primarily be a signal for constitutive up-regulation of gene expression, although a causal relationship has not been firmly established. We are using the model insect Nasonia to investigate the role of DNA methylation in genome evolution and function. This work is part of a highly productive collaboration with Andy Clark and Xu Wang at Cornell University. These studies have shown that methylation in Nasonia does not vary between the sexes, and is stably inherited across generations. We are now interested in identifying potential cis signals for this stable DNA methylation.
- Wang, Xu, JH Werren & AG Clark 2015. Genetic and epigenetic architecture iof sex-biased expression in the jewel wasps Nasonia vitripennis and giraulti. PNAS 112: E3545-E3554.
- 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.
B. Genetics of Species Differences – Behavior, Development, & Reproduction
During evolution, new species arise and diverge in behavior, development, physiology, and genome organization. We have two general goals here, (a) to better understand these processes in their early stages (i.e. microevolution), and (b) to use divergence between species as a tool to identify interesting genes involved in behavior and development. There is growing interest in using the emerging genetic model Nasonia for studies of development and behavior. Below are some of our current projects. Two additional projects not described below, are studies of nuclear-mitochondrial coevolution in laboratory populations, and genome evolution in asexual species.
(1) Memory and the “Genetics of Forgetting”: Although the genetics of memory acquisition has been the subject of intense study, less is known about mechanisms of memory retention and programmed memory loss. We are exploiting the Nasonia system to identify genes involved in memory retention differences between the species, and have an NSF grant to pursue this topic. The project is a collaboration with our colleagues at the University of Wageningen, Hans Smid and Katja Hoedjes. Basically, we have backcrossed two regions that contain genes of large effect on memory retention. By using our well established positional cloning methods (which exploit male haploidy for rapid recombination walking – Loehlin et al 2012), we are conducting fine-scale mapping to identify likely candidate genes . Once identified, follow-up work will investigate how these genes affect memory retention, and whether they may function similarly in other organisms.
- Hoedjes KM, HM Smid, LEM Vet, and JH Werren. 2014. Introgression study reveals two quantitative trait loci involved in interspecific variation in memory retention among Nasonia species. Heredity 113: 542-550. doi: 10.1038/hdy.2014.66.
(2) The Microevolution of Development: As species diverge, so does their development and morphology. The investigate the early stages of this process (i.e. microevolution), systems are needed where recently evolved species are inter-fertile, thus allowing genes to be moved (introgressed) among them for detailed genetic study. This is exactly what we have in Nasonia. By taking advantage of genetic and genomic resources, and the ease of handling this emerging genetic system, we have been able dissect the genetic basis of complex genetic traits, and to use positional cloning methods to clone genes involved in organ size regulation, including cis-regulatory regions affecting organ growth genes.
- 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.
- 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.
- Loehlin et al. 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.
C. Biology of Parasite & Host Interactions
Parasites can range from elements within the genome (e.g. transposons), to microbial parasites and pathogens of plants and animals, to macro-parasites living in or on other organisms. Although the scales differ, there are unifying themes and processes affecting parasite -host interactions across biological levels. We currently focus on three main projects (a) Genetics & Genomics of Parasitoid Insects, (b) Parasitoid Venom Function, Evoluton, and Applications, and (3) Biology of Wolbachia and Other Endosymbionts.
(1) Parasitoid Genetics & Genomics: Parasitoids are insects that lay their eggs in or upon other insects, where the young develop by consuming the “host” to complete their life-cycle. Parasitoids are an incredibly speciose and diverse insects, with estimates of ~200,000 to 500,000 species. They play essential roles in regulating other insects in nature, and therefore also have applications in biological pest control. Our laboratory group is dedicated to increasing basic knowledge and genetic and genomic tools for parasitoids, primarily using the model system Nasonia and its relatives. Please go to the Nasonia link for more information. Below are a couple of relevant papers.
- 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.
- 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.
(2) Parasitoid Venoms – Function, Evolution, and Applications: Parasitoid wasps produce venoms, which they inject into the host. These alter metabolism and physiology of hosts in ways that create a better growth environment for their young. Parasitoid venoms are a potentially immense and largely unexplored pharmacopeia for new drugs and therapeutics. In addition, venoms provide a rich system for studying how genes are recruited for new function during evolution. Among exciting findings are that parasitoid venoms turnover rapidly in closely related species, many are unique proteins not found in other organisms, and yet there is conservation in some of their metabolic effects from flies to human cells, some of which may be relevant to human diseases. Please go to the Venom link for more details. Two recent papers are shown below.
- Mrinalini, AL Siebert, J Wright, E Martinson, D Wheeler, and JH Werren. 2015. Parasitoid venom induces metabolic cascades in fly hosts. Metabolomics 1-17. Doi:10.1007/s11206-014-0697-z
- Siebert, AL, D Wheeler, and JH Werren. 2015. A new approach for investigating venom function applied to venom calreticulin in a parasitoid wasp. Toxicon (Special Issue of Genomic Approaches in Venom Research) doi:10.1016/j.toxicon.2015.08.012.
(3) Wolbachia & Other Endosymbionts: Wolbachia are common and widespread bacteria that are “master manipulators” of arthropod reproduction. We investigate the genetics, ecology, and evolution of Wolbachia and their hosts, to better understand how reproductive parasites shape evolutionary processes. Please go to the Wolbachia link for further details. Recent work has focused on global diversity and genome evolution in Wolbachia. In addition, we conduct computational screens of arthropod genomes, both to detect lateral gene transfers and to look for microbial associates of that are detected as a byproduct of arthropod genome assemblies.
- Werren, J.H., L. Baldo, and M.E. Clark. 2008 Wolbachia: Master Manipulators of Invertebrate Biology. Nature Reviews Microbiology 6:741-751.
- Klein et al. 2016. A novel intracellular mutualistic bacterium in the invasive ant Cardiocondyla obscurior. The ISME Journal 10:376–388; doi:10.1038/ismej.2015.119;doi:10.1038/ismej.2015.119.
Our webpage is also a resource for people interested in applications of Nasonia and/or Wolbachia in research and teaching. Please browse the links to learn more.
University of Rochester, Department of Biology, Rochester NY 14627 (585)275-3889