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Background: Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare.

Background: Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid.

Results: Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides.

Conclusions: The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.

ContributorsRoss, Caitlin R. (Author) / DeFelice, Dominick S. (Author) / Hunt, Greg J. (Author) / Ihle, Kate (Author) / Amdam, Gro (Author) / Rueppell, Olav (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-02-21
Description

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats.

Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits.

Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.

ContributorsSadd, Ben M. (Author) / Barribeau, Seth M. (Author) / Bloch, Guy (Author) / de Graaf, Dirk C. (Author) / Dearden, Peter (Author) / Elsik, Christine G. (Author) / Gadau, Juergen (Author) / Grimmelikhuijzen, Cornelis J. P. (Author) / Hasselmann, Martin (Author) / Lozier, Jeffrey D. (Author) / Robertson, Hugh M. (Author) / Smagghe, Guy (Author) / Stolle, Eckart (Author) / Van Vaerenbergh, Matthias (Author) / Waterhouse, Robert M. (Author) / Bornberg-Bauer, Erich (Author) / Klasberg, Steffen (Author) / Bennett, Anna K. (Author) / Camara, Francisco (Author) / Guigo, Roderic (Author) / Hoff, Katharina (Author) / Mariotti, Marco (Author) / Munoz-Torres, Monica (Author) / Murphy, Terence (Author) / Santesmasses, Didac (Author) / Amdam, Gro (Author) / Beckers, Matthew (Author) / Beye, Martin (Author) / Biewer, Matthias (Author) / Bitondi, Marcia MG (Author) / Blaxter, Mark L. (Author) / Bourke, Andrew FG (Author) / Brown, Mark JF (Author) / Buechel, Severine D. (Author) / Cameron, Rossanah (Author) / Cappelle, Kaat (Author) / Carolan, James C. (Author) / Christiaens, Olivier (Author) / Ciborowski, Kate L. (Author) / Clarke, David F. (Author) / Colgan, Thomas J. (Author) / Collins, David H. (Author) / Cridge, Andrew G. (Author) / Dalmay, Tamas (Author) / Dreier, Stephanie (Author) / du Plessis, Louis (Author) / Duncan, Elizabeth (Author) / Erler, Silvio (Author) / Evans, Jay (Author) / Falcon, Talgo (Author) / Flores, Kevin (Author) / Freitas, Flavia CP (Author) / Fuchikawa, Taro (Author) / Gempe, Tanja (Author) / Hartfelder, Klaus (Author) / Hauser, Frank (Author) / Helbing, Sophie (Author) / Humann, Fernanda (Author) / Irvine, Frano (Author) / Jermiin, Lars S (Author) / Johnson, Claire E. (Author) / Johnson, Reed M (Author) / Jones, Andrew K. (Author) / Kadowaki, Tatsuhiko (Author) / Kidner, Jonathan H. (Author) / Koch, Vasco (Author) / Kohler, Arian (Author) / Kraus, F. Bernhard (Author) / Lattorff, H. Michael G. (Author) / Leask, Megan (Author) / Lockett, Gabrielle A. (Author) / Mallon, Eamonn B. (Author) / Marco Antonio, David S. (Author) / Marxer, Monika (Author) / Meeus, Ivan (Author) / Moritz, Robin FA (Author) / Nair, Ajay (Author) / Napflin, Kathrin (Author) / Nissen, Inga (Author) / Niu, Jinzhi (Author) / Nunes, Francis MF (Author) / Oakeshott, John G. (Author) / Osborne, Amy (Author) / Otte, Marianne (Author) / Pinheiro, Daniel G. (Author) / Rossie, Nina (Author) / Rueppell, Olav (Author) / Santos, Carolina G (Author) / Schmid-Hempel, Regula (Author) / Schmitt, Bjorn D. (Author) / Schulte, Christina (Author) / Simoes, Zila LP (Author) / Soares, Michelle PM (Author) / Swevers, Luc (Author) / Winnebeck, Eva C. (Author) / Wolschin, Florian (Author) / Yu, Na (Author) / Zdobnov, Evgeny M (Author) / Aqrawi, Peshtewani K (Author) / Blakenburg, Kerstin P (Author) / Coyle, Marcus (Author) / Francisco, Liezl (Author) / Hernandez, Alvaro G. (Author) / Holder, Michael (Author) / Hudson, Matthew E. (Author) / Jackson, LaRonda (Author) / Jayaseelan, Joy (Author) / Joshi, Vandita (Author) / Kovar, Christie (Author) / Lee, Sandra L. (Author) / Mata, Robert (Author) / Mathew, Tittu (Author) / Newsham, Irene F. (Author) / Ngo, Robin (Author) / Okwuonu, Geoffrey (Author) / Pham, Christopher (Author) / Pu, Ling-Ling (Author) / Saada, Nehad (Author) / Santibanez, Jireh (Author) / Simmons, DeNard (Author) / Thornton, Rebecca (Author) / Venkat, Aarti (Author) / Walden, Kimberly KO (Author) / Wu, Yuan-Qing (Author) / Debyser, Griet (Author) / Devreese, Bart (Author) / Asher, Claire (Author) / Blommaert, Julie (Author) / Chipman, Ariel D. (Author) / Chittka, Lars (Author) / Fouks, Bertrand (Author) / Liu, Jisheng (Author) / O'Neill, Meaghan P (Author) / Sumner, Seirian (Author) / Puiu, Daniela (Author) / Qu, Jiaxin (Author) / Salzberg, Steven L (Author) / Scherer, Steven E (Author) / Muzny, Donna M. (Author) / Richards, Stephen (Author) / Robinson, Gene E (Author) / Gibbs, Richard A. (Author) / Schmid-Hempel, Paul (Author) / Worley, Kim C (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-04-24
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Description

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies have revealed extensive remodeling of brain, thorax, and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is scarce. To narrow this gap we investigated the proteomic composition of abdominal tissue in the days typically preceding the onset of foraging in honeybee workers.

In order to get a broader representation of possible protein dynamics, we used workers of two genotypes with differences in the age at which they initiate foraging. This approach was combined with RNA interference-mediated downregulation of an insulin/insulin-like signaling component that is central to foraging behavior, the insulin receptor substrate (irs), and with measurements of glucose and lipid levels.
Our data provide new insight into the molecular underpinnings of phenotypic plasticity in the honeybee, invoke parallels with vertebrate metabolism, and support an integrated and irs-dependent association of carbohydrate and lipid metabolism with the transition from in-nest tasks to foraging.

ContributorsChan, Queenie W. T. (Author) / Mutti, Navdeep (Author) / Foster, Leonard J. (Author) / Kocher, Sarah D. (Author) / Amdam, Gro (Author) / Wolschin, Florian (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011-09-28
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Description

Background: Gene bodies are the most evolutionarily conserved targets of DNA methylation in eukaryotes. However, the regulatory functions of gene body DNA methylation remain largely unknown. DNA methylation in insects appears to be primarily confined to exons. Two recent studies in Apis mellifera (honeybee) and Nasonia vitripennis (jewel wasp) analyzed transcription

Background: Gene bodies are the most evolutionarily conserved targets of DNA methylation in eukaryotes. However, the regulatory functions of gene body DNA methylation remain largely unknown. DNA methylation in insects appears to be primarily confined to exons. Two recent studies in Apis mellifera (honeybee) and Nasonia vitripennis (jewel wasp) analyzed transcription and DNA methylation data for one gene in each species to demonstrate that exon-specific DNA methylation may be associated with alternative splicing events. In this study we investigated the relationship between DNA methylation, alternative splicing, and cross-species gene conservation on a genome-wide scale using genome-wide transcription and DNA methylation data.

Results: We generated RNA deep sequencing data (RNA-seq) to measure genome-wide mRNA expression at the exon- and gene-level. We produced a de novo transcriptome from this RNA-seq data and computationally predicted splice variants for the honeybee genome. We found that exons that are included in transcription are higher methylated than exons that are skipped during transcription. We detected enrichment for alternative splicing among methylated genes compared to unmethylated genes using fisher’s exact test. We performed a statistical analysis to reveal that the presence of DNA methylation or alternative splicing are both factors associated with a longer gene length and a greater number of exons in genes. In concordance with this observation, a conservation analysis using BLAST revealed that each of these factors is also associated with higher cross-species gene conservation.

Conclusions: This study constitutes the first genome-wide analysis exhibiting a positive relationship between exon-level DNA methylation and mRNA expression in the honeybee. Our finding that methylated genes are enriched for alternative splicing suggests that, in invertebrates, exon-level DNA methylation may play a role in the construction of splice variants by positively influencing exon inclusion during transcription. The results from our cross-species homology analysis suggest that DNA methylation and alternative splicing are genetic mechanisms whose utilization could contribute to a longer gene length and a slower rate of gene evolution.

ContributorsFlores, Kevin (Author) / Wolschin, Florian (Author) / Corneveaux, Jason J. (Author) / Allen, April N. (Author) / Huentelman, Matthew J. (Author) / Amdam, Gro (Author) / College of Liberal Arts and Sciences (Contributor)
Created2012-09-15
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Description

We investigate near-field radiative heat transfer between Indium Tin Oxide (ITO) nanowire arrays which behave as type 1 and 2 hyperbolic metamaterials. Using spatial dispersion dependent effective medium theory to model the dielectric function of the nanowires, the impact of filling fraction on the heat transfer is analyzed. Depending on

We investigate near-field radiative heat transfer between Indium Tin Oxide (ITO) nanowire arrays which behave as type 1 and 2 hyperbolic metamaterials. Using spatial dispersion dependent effective medium theory to model the dielectric function of the nanowires, the impact of filling fraction on the heat transfer is analyzed. Depending on the filling fraction, it is possible to achieve both types of hyperbolic modes. At 150 nm vacuum gap, the heat transfer between the nanowires with 0.5 filling fraction can be 11 times higher than that between two bulk ITOs. For vacuum gaps less than 150 nm the heat transfer increases as the filling fraction decreases. Results obtained from this study will facilitate applications of ITO nanowires as hyperbolic metamaterials for energy systems.

ContributorsChang, Jui-Yung (Author) / Basu, Soumyadipta (Author) / Wang, Liping (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-02-07
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Description

Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vitellogenin is the carrier of

Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vitellogenin is the carrier of immune elicitors. Using the honey bee, Apis mellifera, model system, we demonstrate with microscopy and western blotting that vitellogenin binds to bacteria, both Paenibacillus larvae – the gram-positive bacterium causing American foulbrood disease – and to Escherichia coli that represents gram-negative bacteria. Next, we verify that vitellogenin binds to pathogen-associated molecular patterns; lipopolysaccharide, peptidoglycan and zymosan, using surface plasmon resonance. We document that vitellogenin is required for transport of cell-wall pieces of E. coli into eggs by imaging tissue sections. These experiments identify vitellogenin, which is distributed widely in oviparous species, as the carrier of immune-priming signals. This work reveals a molecular explanation for trans-generational immunity in insects and a previously undescribed role for vitellogenin.

ContributorsSalmela, Heli (Author) / Amdam, Gro (Author) / Freitak, Dalial (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-07-31
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Description

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

ContributorsWallace, Robert G. (Author) / Twomey, Laura C. (Author) / Custaud, Marc-Antoine (Author) / Moyna, Niall (Author) / Cummins, Philip M. (Author) / Mangone, Marco (Author) / Murphy, Ronan P. (Author) / Biodesign Institute (Contributor)
Created2015-11-24
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Description

Cubic (space group: Fmm) iridium phosphide, Ir2P, has been synthesized at high pressure and high temperature. Angle-dispersive synchrotron X-ray diffraction measurements on Ir2P powder using a diamond-anvil cell at room temperature and high pressures (up to 40.6 GPa) yielded a bulk modulus of B[subscript 0] = 306(6) GPa and its pressure derivative B0′ = 6.4(5).

Cubic (space group: Fmm) iridium phosphide, Ir2P, has been synthesized at high pressure and high temperature. Angle-dispersive synchrotron X-ray diffraction measurements on Ir2P powder using a diamond-anvil cell at room temperature and high pressures (up to 40.6 GPa) yielded a bulk modulus of B[subscript 0] = 306(6) GPa and its pressure derivative B0′ = 6.4(5). Such a high bulk modulus attributed to the short and strongly covalent Ir-P bonds as revealed by first – principles calculations and three-dimensionally distributed [IrP4] tetrahedron network. Indentation testing on a well–sintered polycrystalline sample yielded the hardness of 11.8(4) GPa. Relatively low shear modulus of ~64 GPa from theoretical calculations suggests a complicated overall bonding in Ir2P with metallic, ionic, and covalent characteristics. In addition, a spin glass behavior is indicated by magnetic susceptibility measurements.

ContributorsWang, Pei (Author) / Wang, Yonggang (Author) / Wang, Liping (Author) / Zhang, Xinyu (Author) / Yu, Xiaohui (Author) / Zhu, Jinlong (Author) / Wang, Shanmin (Author) / Qin, Jiaqian (Author) / Leinenweber, Kurt (Author) / Chen, Haihua (Author) / He, Duanwei (Author) / Zhao, Yusheng (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2016-02-24
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Description

Background: Lizards are evolutionarily the most closely related vertebrates to humans that can lose and regrow an entire appendage. Regeneration in lizards involves differential expression of hundreds of genes that regulate wound healing, musculoskeletal development, hormonal response, and embryonic morphogenesis. While microRNAs are able to regulate large groups of genes, their

Background: Lizards are evolutionarily the most closely related vertebrates to humans that can lose and regrow an entire appendage. Regeneration in lizards involves differential expression of hundreds of genes that regulate wound healing, musculoskeletal development, hormonal response, and embryonic morphogenesis. While microRNAs are able to regulate large groups of genes, their role in lizard regeneration has not been investigated.

Results: MicroRNA sequencing of green anole lizard (Anolis carolinensis) regenerating tail and associated tissues revealed 350 putative novel and 196 known microRNA precursors. Eleven microRNAs were differentially expressed between the regenerating tail tip and base during maximum outgrowth (25 days post autotomy), including miR-133a, miR-133b, and miR-206, which have been reported to regulate regeneration and stem cell proliferation in other model systems. Three putative novel differentially expressed microRNAs were identified in the regenerating tail tip.

Conclusions: Differentially expressed microRNAs were identified in the regenerating lizard tail, including known regulators of stem cell proliferation. The identification of 3 putative novel microRNAs suggests that regulatory networks, either conserved in vertebrates and previously uncharacterized or specific to lizards, are involved in regeneration. These findings suggest that differential regulation of microRNAs may play a role in coordinating the timing and expression of hundreds of genes involved in regeneration.

ContributorsHutchins, Elizabeth (Author) / Eckalbar, Walter (Author) / Wolter, Justin (Author) / Mangone, Marco (Author) / Kusumi, Kenro (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-05-05
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Description

MicroRNAs (miRNAs) regulate gene output by targeting degenerate elements in mRNAs and have undergone drastic expansions in higher metazoan genomes. The evolutionary advantage of maintaining copies of highly similar miRNAs is not well understood, nor is it clear what unique functions, if any, miRNA family members possess. Here, we study

MicroRNAs (miRNAs) regulate gene output by targeting degenerate elements in mRNAs and have undergone drastic expansions in higher metazoan genomes. The evolutionary advantage of maintaining copies of highly similar miRNAs is not well understood, nor is it clear what unique functions, if any, miRNA family members possess. Here, we study evolutionary patterns of metazoan miRNAs, focusing on the targeting preferences of the let-7 and miR-10 families. These studies reveal hotspots for sequence evolution with implications for targeting and secondary structure. High-throughput screening for functional targets reveals that each miRNA represses sites with distinct features and regulates a large number of genes with cooperative function in regulatory networks. Unexpectedly, given the high degree of similarity, single-nucleotide changes grant miRNA family members with distinct targeting preferences. Together, our data suggest complex functional relationships among miRNA duplications, novel expression patterns, sequence change, and the acquisition of new targets.

ContributorsWolter, Justin (Author) / Le, Hoai Huang Thi (Author) / Linse, Alexander (Author) / Godlove, Victoria (Author) / Nguyen, Thuy-Duyen (Author) / Kotagama, Kasuen (Author) / Lynch, Cherie Alissa (Author) / Rawls, Alan (Author) / Mangone, Marco (Author) / Biodesign Institute (Contributor)
Created2016-12-07