Human Biology Division & Basic Sciences Division, Fred Hutchinson Cancer Research Centercontact me: firstname.lastname@example.org
research interests | peer reviewed publications | résumé | curriculum vitae | video of electric fish behavior | science writing and editorial contributions to Science Spotlight (a science news periodical)
The evolution of biological diversity depends on three interdependent processes: (i) adaptation within lineages; (ii) the splitting of lineages, or speciation; and (iii) the origin of novelty. While evolutionary biologists have made much progress in understanding the ecological causes of speciation in many different systems, the field has barely begun to uncover the genetic basis of ecological speciation. I am particularly interested in studying genes underlying sexual signals, mating preferences, and other behaviors related to pre-mating reproductive isolation. These aspects of animal speciation merge naturally with my broader interests in the evolution of animal communication. Understanding the origins of new modes of communication requires that we also understand, more generally, how innovative structures and physiological systems evolve de novo. Investigating genetic changes associated with novelty remains one of evolutionary biology's greatest challenges, with little insight into this process being offered by well-investigated cases of regressive trait loss.
Currently, my main project with Katie Peichel, Dolph Schluter, and Gina Conte investigates the genetic basis of parallel ecological speciation between benthic and limnetic sticklebacks. I started this project with Dolph at the University of British Columbia (UBC) in 2007; more recently, I received postdoctoral NRSA funds from NIH to continue this project with Katie at the Fred Hutchinson Cancer Research Center in Seattle, in collaboration with Dolph and Gina at UBC. In the Schluter Lab, Gina and I created a number of mapping populations of F2 intercross hybrids between sympatric benthic and limnetic sticklebacks endemic to each of two lakes in British Columbia (Paxton and Priest: see above). The hybrids were reared under fully natural conditions in experimental ponds at UBC. We have measured a number of F2 phenotypes related to important ecological differences between the parental species (e.g., functional morphology, stable isotopes of carbon and nitrogen, habitat choice). In the summer of 2011, we completed fieldwork needed to measure behaviors contributing to pre-mating reproductive isolation: e.g., nesting habitat choice of F2 males; and F2 female mating preferences for benthic versus limnetic males assessed by genetically fingerprinting offspring. Recently, our project received additional NIH funds needed to genotype all F2s using an array of 1,536 SNPs. We are in the process of testing the genetic architectures underlying ecological speciation for species pairs in both Paxton and Priest Lakes. We are particularly interested in asking whether the same QTL – either pleiotropic or closely linked genes – simultaneously govern ecological traits under divergent natural selection and behaviors contributing to reproductive isolation. Such a genetic architecture would favor rapid speciation under gene flow. We are also testing whether there is parallelism in the genetic architectures of species differences between the two lakes. We presented our initial results at the 2012 Evolution Conference in Ottawa, Canada, and at the 2012 International Conference on Stickleback Behavior and Evolution, which took place on Bainbridge Island near Seattle. The first manuscripts for this project are currently in the works.
In addition to research on speciation genetics, I also investigate the role of communication in speciation, the origins of novel communication systems, and the effects of neural innovations on the tempo and breadth of species radiation. I do so using weakly-electric fishes. In one of the most remarkable cases of convergence in the Animal Kingdom, speciose groups of electric fish (mormyroids and gymnotiforms) arose independently in Africa and South America, respectively. I recently led an effort to test whether a duplicated voltage-gated sodium channel gene (Scn4aa) directly contributed to independently-derived electric organs in mormyroids and gymnotiforms. Myogenic electric organs (EOs) produce electrical communication signals in both groups. EO is composed of cells called electrocytes, which are developmentally derived from skeletal muscle myoblasts and show striking similarities in structure and physiology between groups. To function, electrocytes require voltage-gated sodium channels (see the figure, below), two paralogs of which (Scn4aa and Scn4ab) I and co-authors Derrick Zwickl, Ying Lu, and Harold Zakon investigated in a large number of electrogenic and non-electrogenic fishes. We tested three predictions of our hypothesis that Scn4aa directly contributed to the parallel origins of this novel organ of communication. Our findings provide evidence in support of all three predictions, demonstrating that gene duplication can contribute to strikingly similar innovations even after extremely long waiting periods between gene duplication and the origins of novelty. We also found that amino acid replacements caused by diversifying natural selection on Scn4aa in electric fish occur at the same residues where deleterious substitutions in paralogs cause cardiac or neurological disease in humans (e.g., long QT syndrome). Read more about these findings in Arnegard et al., 2010 (PNAS 107: 22172-22177).
The origins of electrical communication are examples of 'key innovations' that have directly contributed to the independent evolutionary radiations of gymnotiforms and mormyroids. I also recently led a project showing that electric organ discharges (EODs) have evolved much faster than ecological traits in the Paramormyrops species flock of mormyroid electric fishes radiating in west-Central Africa (see the figure, below). Based on the prior work of myself and others, we know that EODs function as courtship signals underlying mate recognition, and that EODs exhibit dramatic sexual dimorphism in many mormyroids, including Paramormyrops. Together, these findings implicate sexual selection as a potentially important driver of mormyroid speciation (within specific lineages). Given certain features of the electrical communication modality, our findings also suggest that 'opportunity' in the communication landscape can augment rates of phenotypic divergence and species radiation by sexual selection, analogous to the well established role of 'ecological opportunity' in adaptive radiation. Read more about this research in Arnegard et al., 2010 (Am. Nat. 176: 335-356). Co-authors: Pete McIntyre, Luke Harmon, Miriam Zelditch, Will Crampton, Justin Davis, John Sullivan, Sébastien Lavoué, and Carl Hopkins.
More recently, Bruce Carlson, several of his lab members, Luke Harmon, and I investigated the evolutionary consequences of neural novelties on the sensory and motor sides of electrical communication in mormyroid fishes (Carlson et al., 2011. Science 332: 583-586). We found that the origin of developmental flexibility in one aspect of electrocyte morphology (the stalk system) resulted in an enhanced capacity for evolutionary divergence in EOD waveforms on the motor (or sender) side of electrical communication. On the receiver side, change in a sensory region of the brain established a newfound ability to detect subtle variation in electric signals for the purpose of species and sex recognition. In combination, these novel enhancements of electrical communication triggered dramatic increases in both the rate of EOD divergence and the rate of species diversification in the largest lineage of mormyroid fishes, which we now call 'clade A'. As Bruce and I go on to discuss (Carlson & Arnegard, 2011. Communicative & Integrative Biology 4: 720-725), neural innovations and resulting opportunities in the communication landscape may have played a general role in augmenting species radiation in a variety of animal groups. Examples might be found among orthopteran insects, anuran amphibians, songbirds, and bats, in addition to other animal groups.
*The first two authors contributed equally to these studies.
Video of Electric Fish Behavior — filmed under natural conditions in Africa.
|Arnegard, M. E. 2013. Dynamics of herpes reactivation in the genital tract. Jun-17 issue of Science Spotlight: Intensive sampling and mathematical modeling show that HSV-2 reactivation is characterized by very rapid viral expansion and immune containment at multiple sites.|
|Arnegard, M. E. 2013. Newly discovered class of cytotoxic T cells suppresses genital herpes. Jun-17 issue of Science Spotlight: Scientists identify a new type of tissue-resident T cell (CD8αα+) that plays a key role in immune surveillance and initial containment of genital herpes reactivation.|
|Arnegard, M. E. 2013. Stabilizing mutations allow subsequent immune escape during flu evolution. May-20 issue of Science Spotlight: Nucleoprotein mutations beneficial to H3N2 flu viruses can only be accessed in 'protein space' when other enabling mutations enhance the protein's stability.|
|Arnegard, M. E. 2013. Validation of biomarkers for active surveilance of prostate cancer. May-20 issue of Science Spotlight: Each of two biomarkers stratifies baseline risk of aggressive prostate cancer, yet more research is needed to integrate these markers into treatment decisions.|
|Arnegard, M. E. 2013. Combinatorial sample pooling assigns rare DNA variants to known individuals. Apr-15 issue of Science Spotlight: Chen et al. use their V-Sieve algorithm to screen for dozens of rare, new genetic variants in the CRP locus and simultaneously identify individuals carrying them.|
|Arnegard, M. E. 2013. Upgraded statistical machinery for analyzing upcoming HIV vaccine trials. Apr-15 issue of Science Spotlight: New technique for estimating vaccine efficacy as a function of vaccine-induced immune responses improves evaluation of surrogate markers in future HIV vaccine trials.|
|Arnegard, M. E. 2013. Ancient origins for the simian relatives of modern HIV. Mar-18 issue of Science Spotlight: Molecular evolutionary analyses and infectivity tests reveal ancient origins of simian lentiviruses, which co-evolved with a host immunity factor on multiple fronts.|
|Arnegard, M. E. 2013. Ecology drives biofilm patterning, potentially affecting its health impacts. Mar-18 issue of Science Spotlight: Simulations and tests with yeast communities engineered to compete, or cooperate, via metabolite limitations reveal new ecological 'rules' governing biofilm geometry.|
|Arnegard, M. E. 2013. Imaging a fungal lung infection that affects the immune-compromised. Feb-18 issue of Science Spotlight: Hohl Lab tags Aspergillus with a viability reporter transgene and a covalently linked fluorophore to show how neutrophils kill conidia at single-encounter resolution.|
|Arnegard, M. E. 2013. When does an HIV intervention outperform the placebo in a community setting? Feb-18 issue of Science Spotlight: A deterministic model formulated by Dimitrov and colleagues revelas important trade-offs in the design of clinical trials for investigating HIV prevention strategies.|
|Arnegard, M. E. 2013. Feline leukemia virus inhibits thiamine uptake, with pathological consequences. Jan-21 issue of Science Spotlight: Feline leukemia virus (FeLV) subgroup A inhibits thiamine uptake in cat cells, which may contribute to FeLV pathogenicity in both domestic and wild cats.|
|Arnegard, M. E. 2013. Response of HIV-1-infected children in Kenya to antiretroviral therapy. Jan-21 issue of Science Spotlight: When quantification of viral load is not an option for HIV-1-infected children, an unwanted delay in second-line treatment often promotes multi-class drug resistance.|
|Arnegard, M. E. 2012. Multi-assay algorithm for monitoring the HIV pandemic's leading edge. Dec-17 issue of Science Spotlight: Researchers develop a new hierarchical approach for estimating HIV incidence and find it outperforms other cross-sectional approaches by giving fewer false positives.|
|Arnegard, M. E. 2012. Viral protein fragmentation may broaden T-cell responses to HIV vaccines. Dec-17 issue of Science Spotlight: Researchers find that fragmenting the HIV Gag structural protein may help maximize immune responses to T-cell-based HIV vaccines.|
|Arnegard, M. E. 2012. Inheritance of two benign genetic variants causes a muscular dystrophy. Nov-19 issue of Science Spotlight: D4Z4 contraction-independent facioscapulohumeral dystrophy (FSHD) is caused by inheritance of both a disease-permissive D4Z4 allele and a mutated form of SMCHD1.|
|Arnegard, M. E. 2012. Sieve analysis shows partial efficacy of an HIV-1 vaccine tested in Thailand. Nov-19 issue of Science Spotlight: Analysis of breakthrough viruses in recipients of a vaccine regimen (ALVAC-HIV prime and AIDSVAX B/E boost) identifies signatures of protection from HIV-1 infection.|
|Arnegard, M. E. 2012. Development of a guinea pig model for congenital CMV infection. Oct-22 issue of Science Spotlight: A guinea pig CMV protein, gp145, binds dsRNA and attenuates the antiviral PKR pathway in a way that resembles the action of TRS1 expressed by human CMV.|
|Arnegard, M. E. 2012. The vast, interconnected regulatory landscape of the human genome. Oct-22 issue of Science Spotlight: Researchers identify millions of genetic regulatory elements once thought to be junk DNA, and they begin to decode the combinatorial logic of the human 'regulome'.|
|Arnegard, M. E. 2012. Antibodies with distinct specificities neutralize diverse HIV-1 variants. Sep-17 issue of Science Spotlight: A mixture of antibodies targeting the CD4 binding site and the V3 loop of the HIV-1 envelope spike neutralizes a vast majority of recently transmitted HIV-1 viruses.|
|Arnegard, M. E. 2012. Insights into Holliday junction resolution and chromosome segregation in yeast. Sep-17 issue of Science Spotlight: In fission yeast the resolution of Holliday junctions by Mus81-Eme1, which is necessary for proper meiosis, depends on Nse5-Nse6 of the Smc5-Smc6 genome stability complex.|
|Arnegard, M. E. 2012. Genetic insights emerge from the shattered remains of lost species. Aug-20 issue of Science Spotlight: Researchers in the Human Biology Division use admixture mapping in a vertebrate hybrid swarm to show how the same genomic regions influence different complex traits.|
|Arnegard, M. E. 2012. Rampant replacements of heterochromatin-binding proteins in fly gonads. Aug-20 issue of Science Spotlight: Levine et al. discover a plethora of new HP1 genes with restricted germline expression in flies and theorize on the forces responsible for this burst of innovation.|
|Arnegard, M. E. 2012. Dab2 recruits EH domain proteins to regulate clathrin-mediated endocytosis. Jul-16 issue of Science Spotlight: Research on integrin β1 endocytosis shows that efficient internalization of clathrin-coated pits requires adaptors to be bound to cargo and EH domain proteins.|
|Arnegard, M. E. 2012. How to drug "undruggable" cancers: functional genomics points the way. Jul-16 issue of Science Spotlight: The Grandori Lab rapidly achieves successful preclinical tumor regression via a high throughput screen for synthetic lethal interactions with MYC over-expression.|
|Arnegard, M. E. 2012. A new model of spindle checkpoint silencing. Jun-18 issue of Science Spotlight: The kinase Mps1 and the phosphatase PP1 act in opposition to regulate complex signaling events responsible for proper checkpoint function and chromosome segregation.|
|Arnegard, M. E. 2012. New online platform for well-characterized meganucleases. Jun-18 issue of Science Spotlight: Stoddard Lab develops an online catalog of homing endonucleases with validated properties, as well as a powerful search engine for identifying potential DNA targets.|
|Arnegard, M. E. 2012. A meeting of cell lineage and regulatory networks specifies differentiation. May-21 issue of Science Spotlight: Binding of NEUROD2 and MYOD to private E-boxes is associated with gene transcription, while binding to shared motifs tends to cause epigenetic chromatin modifications.|
|Arnegard, M. E. 2012. Powerful HIV disease prognosis despite sparse and irregular sampling. May-21 issue of Science Spotlight: Holte and colleagues demonstrate that functional principal component analysis provides an effective and efficient summary of sparsely sampled HIV loads and CD4 counts.|
|Arnegard, M. E. 2012. How exactly does the locus control region regulate beta-globin genes? Apr-16 issue of Science Spotlight: LCR hypersensitive sites mediate the association of the β-globin locus with transcription factories and the enhancement of actively transcribed alleles by different mechanisms.|
|Arnegard, M. E. 2012. Wound healing initiated by a ubiquitous connexin and a MAGUK protein. Apr-16 issue of Science Spotlight: The gap junction protein, Cx43, and calcium/calmodulin-dependent serine kinase, CASK, interact to initiate skin cell migration during wound healing.|
|Arnegard, M. E. 2012. CMVs counter-evolve with the rapidly changing host antiviral PKR gene. Mar-19 issue of Science Spotlight: Species specificity of PKR antagonism by CMV TRS1 results from CMVs playing a role in complex evolutionary 'arms races' between the PKR pathway and pathogenic viruses.|
|Arnegard, M. E. 2012. History of primate-SIV conflict drives adaptive diversification of A3G. Mar-19 issue of Science Spotlight: Despite being generally asymptomatic in their natural hosts, SIVs select for Vif-resistant forms of A3G in African green monkeys, driving Vif counter-evolution.|
|Arnegard, M. E. 2012. Comprehensive study illuminates regulation and significance of NAGNAG splicing. Feb-20 issue of Science Spotlight: New faculty member shows how alternative splicing of RNA triplets is regulated and generates proteome diversity at developmental and evolutionary timescales.|
|Arnegard, M. E. 2012. DNA binding action of a TAL effector captured in 3D. Feb-20 issue of Science Spotlight: Stoddard Lab solves the crystal structure of a TAL effector bound to its DNA target, laying the foundation for broad applications of this powerful genetic tool.|
|Arnegard, M. E. 2012. Epistasis and the genetic basis of species formation in Drosophila pseudoobscura. Jan-23 issue of Science Spotlight: Basic Sciences Division postdoctoral fellow, Dr. Nitin Phadnis, shows how complex negative gene interactions in a largely interconnected genetic network underlie male sterility and segregation distortion.|
|Arnegard, M. E. 2012. Global gene inhibition during heat shock via reduced stalled Pol II and nucleosome turnover. Jan-23 issue of Science Spotlight: Researchers better understand general mechanisms of gene regulation using novel, in house tools to measure chromatin landscape dynamics in a classic heat shock response framework.|
Arnegard, M. E. 2011. Greater focus for fuzzy epigenomes. Dec-12 issue of Science Spotlight: Henikoff Lab devises a new strategy for characterizing epigenomes at single base-pair resolution, promising to yield many insights into nucleosome dynamics.
|Arnegard, M. E. 2011. Increased longevity in an extreme environment is orchestrated by hif-1 and skn-1. Dec-12 issue of Science Spotlight: In nematodes exposed to hydrogen sulfide, two transcription factors coordinate a broad transcriptional response that globally reorganizes protein homeostasis networks and prolongs life.|
Arnegard, M. E. 2011. Certain beta-HPVs target p300 for degradation, likely disrupting many cellular signaling pathways. Nov-14 issue of Science Spotlight: Galloway Lab study suggests that beta-human papillomaviruses may induce skin cancer by a slightly different route than their better-known alpha-cousins.
Arnegard, M. E. 2011. Mathematical model for controllability of dynamic genome networks. Nov-14 issue of Science Spotlight: Development of a systems theory framework for cell differentiation sheds light on dynamic network control, in general, and may one day help to redirect cancer cells along non-pathological trajectories.
Arnegard, M. E. 2011. Homing in on the genetic basis of adaptive pigmentation differences in a new vertebrate model system. Oct-17 issue of Science Spotlight: Researchers identify parallel differences in pigmentation patterning between local marine and freshwater populations of threespine stickleback, and achieve significant steps towards dissecting the genetic architecture of differences in the fish's appearance.
|Arnegard, M. E. 2011. Recognizing the breadth and biological significance of a mechanism underlying microRNA diversity. Oct-17 issue of Science Spotlight: New findings suggest that we may have only glimpsed the tip of a larger iceberg when it comes to the generation of microRNA transcriptome complexity via 3' nucleotide addition, as well as assessing the biological importance of this source of miRNA variation.|
Arnegard, M. E. et al. 2012. Sixth sense – an electric one. Dec. 2012 issue of Science First Hand Journal. Published in Novosibirsk, Russia, by the Siberian Branch of the Russian Academy of Sciences. Written in English by Arnegard et al. and translated into Russian by the editorial staff of Science First Hand Journal.
Page Last Updated: 17 June 2013
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