@article{mclamb_gibson_overman_stahl_moeser_2013, title={Early Weaning Stress in Pigs Impairs Innate Mucosal Immune Responses to Enterotoxigenic E. coli Challenge and Exacerbates Intestinal Injury and Clinical Disease}, volume={8}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0059838}, abstractNote={Background and Aims The clinical onset and severity of intestinal disorders in humans and animals can be profoundly impacted by early life stress. Here we investigated the impact of early weaning stress in pigs on intestinal physiology, clinical disease, and immune response to subsequent challenge with enterotoxigenic F18 E. coli (ETEC). Methodology Pigs weaned from their dam at 16 d, 18 d, and 20 d of age were given a direct oral challenge of F18 ETEC at 26 d of age. Pigs were monitored from days 0 to 4 post-infection for clinical signs of disease. On Day 4 post-ETEC challenge, ileal barrier function, histopathologic and inflammatory cytokine analysis were performed on ileal mucosa. Results Early weaned pigs (16 d and 18 d weaning age) exhibited a more rapid onset and severity of diarrhea and reductions in weight gain in response to ETEC challenge compared with late weaned pigs (20 d weaning age). ETEC challenge induced intestinal barrier injury in early weaned pigs, indicated by reductions in ileal transepithelial electrical resistance (TER) and elevated FD4 flux rates, in early weaned pig ileum but not in late weaned pigs. ETEC-induced marked elevations in IL-6 and IL-8, neutrophil recruitment, and mast cell activation in late-weaned pigs; these responses were attenuated in early weaned pigs. TNF levels elevated in ETEC challenged ileal mucosa from early weaned pigs but not in other weaning age groups. Conclusions These data demonstrate the early weaning stress can profoundly alter subsequent immune and physiology responses and clinical outcomes to subsequent infectious pathogen challenge. Given the link between early life stress and gastrointestinal diseases of animals and humans, a more fundamental understanding of the mechanisms by which early life stress impacts subsequent pathophysiologic intestinal responses has implications for the prevention and management of important GI disorders in humans and animals.}, number={4}, journal={PLOS ONE}, author={McLamb, Brittney L. and Gibson, Amelia J. and Overman, Elizabeth L. and Stahl, Chad and Moeser, Adam J.}, year={2013}, month={Apr} }
 @article{dworkin_anderson_idaghdour_parker_stone_gibson_2011, title={The Effects of Weak Genetic Perturbations on the Transcriptome of the Wing Imaginal Disc and Its Association With Wing Shape in Drosophila melanogaster}, volume={187}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.110.125922}, abstractNote={Abstract
               A major objective of genomics is to elucidate the mapping between genotypic and phenotypic space as a step toward understanding how small changes in gene function can lead to elaborate phenotypic changes. One approach that has been utilized is to examine overall patterns of covariation between phenotypic variables of interest, such as morphology, physiology, and behavior, and underlying aspects of gene activity, in particular transcript abundance on a genome-wide scale. Numerous studies have demonstrated that such patterns of covariation occur, although these are often between samples with large numbers of unknown genetic differences (different strains or even species) or perturbations of large effect (sexual dimorphism or strong loss-of-function mutations) that may represent physiological changes outside of the normal experiences of the organism. We used weak mutational perturbations in genes affecting wing development in Drosophila melanogaster that influence wing shape relative to a co-isogenic wild type. We profiled transcription of 1150 genes expressed during wing development in 27 heterozygous mutants, as well as their co-isogenic wild type and one additional wild-type strain. Despite finding clear evidence of expression differences between mutants and wild type, transcriptional profiles did not covary strongly with shape, suggesting that information from transcriptional profiling may not generally be predictive of final phenotype. We discuss these results in the light of possible attractor states of gene expression and how this would affect interpretation of covariation between transcriptional profiles and other phenotypes.}, number={4}, journal={GENETICS}, author={Dworkin, Ian and Anderson, Julie A. and Idaghdour, Youssef and Parker, Erin Kennerly and Stone, Eric A. and Gibson, Greg}, year={2011}, month={Apr}, pages={1171–U314} }
 @misc{need_attix_mcevoy_cirulli_linney_hunt_ge_heinzen_maia_shianna_et al._2009, title={A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB}, volume={18}, number={23}, journal={Human Molecular Genetics}, author={Need, A. C. and Attix, D. K. and McEvoy, J. M. and Cirulli, E. T. and Linney, K. L. and Hunt, P. and Ge, D. L. and Heinzen, E. L. and Maia, J. M. and Shianna, K. V. and et al.}, year={2009}, pages={4650–4661} }
 @article{goering_hunt_heighington_busick_pennings_hermisson_kumar_gibson_2009, title={Association of orthodenticle with Natural Variation for Early Embryonic Patterning in Drosophila melanogaster}, volume={312B}, ISSN={["1552-5015"]}, DOI={10.1002/jez.b.21299}, abstractNote={AbstractAlthough it is well established that cis‐acting regulatory variation contributes to morphological evolution between species, few concrete examples of polymorphism affecting developmental patterning within species have been demonstrated. Early embryogenesis in Drosophila is initiated by a gradient of Bicoid morphogen activity that results in differential expression of multiple target genes. In a screen for genetic variation affecting this process, we surveyed 96 wild‐type lines of Drosophila melanogaster for polymorphisms in binding sites within 16 Bicoid cis‐regulatory response elements. One common polymorphism in the orthodenticle (otd) early head enhancer is associated with a complex series of indels/substitutions that define two distinct haplotypes. The middle region of this enhancer exhibits an unusual pattern of nucleotide diversity that does not easily fit into standard models of selection and demography. Population Gene Expression Maps, generated by extracting binary expression profiles from normalized embryo images, revealed a ventral reduction of otd transcript abundance in one of the haplotypes that was recapitulated in expression of transgenic constructs containing the two alleles. We thus demonstrate that even a process as robust as early developmental patterning is affected by standing genetic variation, intriguingly involving otd, whose morphogenetic function bicoid is thought to have displaced during dipteran evolution. J. Exp. Zool. (Mol. Dev. Evol.) 312B:841–854, 2009. © 2009 Wiley‐Liss, Inc.}, number={8}, journal={JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION}, author={Goering, Lisa M. and Hunt, Priscilla K. and Heighington, Cassandra and Busick, Christopher and Pennings, Pleuni S. and Hermisson, Joachim and Kumar, Sudhir and Gibson, Greg}, year={2009}, month={Dec}, pages={841–854} }
 @article{idaghdour_czika_shianna_lee_visscher_martin_miclaus_jadallah_goldstein_wolfinger_et al._2010, title={Geographical genomics of human leukocyte gene expression variation in southern Morocco}, volume={42}, ISSN={["1546-1718"]}, DOI={10.1038/ng.495}, abstractNote={Greg Gibson and colleagues report an analysis of gene expression variation in relation to environmental geography and ethnicity in blood leukocyte samples from individuals in rural and urban southern Morocco. The study determined the contributions of geography and ethnicity to associations between genotypes and transcript abundance. Studies of the genetics of gene expression can identify expression SNPs (eSNPs) that explain variation in transcript abundance. Here we address the robustness of eSNP associations to environmental geography and population structure in a comparison of 194 Arab and Amazigh individuals from a city and two villages in southern Morocco. Gene expression differed between pairs of locations for up to a third of all transcripts, with notable enrichment of transcripts involved in ribosomal biosynthesis and oxidative phosphorylation. Robust associations were observed in the leukocyte samples: cis eSNPs (P < 10−08) were identified for 346 genes, and trans eSNPs (P < 10−11) for 10 genes. All of these associations were consistent both across the three sample locations and after controlling for ancestry and relatedness. No evidence of large-effect trans-acting mediators of the pervasive environmental influence was found; instead, genetic and environmental factors acted in a largely additive manner.}, number={1}, journal={NATURE GENETICS}, author={Idaghdour, Youssef and Czika, Wendy and Shianna, Kevin V. and Lee, Sang H. and Visscher, Peter M. and Martin, Hilary C. and Miclaus, Kelci and Jadallah, Sami J. and Goldstein, David B. and Wolfinger, Russell D. and et al.}, year={2010}, month={Jan}, pages={62–U79} }
 @book{gibson_2009, title={It takes a genome: How a clash between our genes and modern life is making us sick}, ISBN={9780137137466}, publisher={Upper Saddle River, N.J. : Pearson Education}, author={Gibson, G.}, year={2009} }
 @article{kennerly_idaghdour_olby_munana_gibson_2009, title={Pharmacogenetic association study of 30 genes with phenobarbital drug response in epileptic dogs}, volume={19}, ISSN={1744-6872}, url={http://dx.doi.org/10.1097/fpc.0b013e3283307cba}, DOI={10.1097/FPC.0b013e3283307cba}, abstractNote={BackgroundEpilepsy, with a prevalence as high as 6%, is the most common neurological disorder in dogs. Although several antiepileptic drugs are in common use, in one-third of all epileptic dogs, adequate seizure control is not achieved with a single medication, and hence a combinatorial drug treatment must be adopted. Exploration of the genetic mechanisms involved in drug response may provide better treatment options for epileptic patients. Methods and resultsA custom Illumina BeadChip was designed for high throughput genotyping of 384 single nucleotide polymorphisms in 30 genes involved in drug metabolism, drug targeting, and drug transport. A case–control association study of 125 epileptic dogs identified five genes with suggestive association to phenobarbital drug response: KCNQ3, P=0.0003; SNC2A2, P=0.0008; EPOX HYD, P=0.0005; ABCC4, P=0.0091; and GABRA2, P=0.0130. These associations are not significant after adjustment for multiple comparisons, but on functional grounds may tag strong candidate genes. The study was powered to detect alleles with at least 3.5-fold additive increases in responsiveness. A combined area under the curve value of 0.74 from receiver operating curve analysis also provides suggestive support for their consideration as canine pharmacogenetic markers. ConclusionFurther replication and assessment of breed specificity is required before these markers can be considered as predictive of responsiveness to phenobarbital in dogs.}, number={12}, journal={Pharmacogenetics and Genomics}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Kennerly, Erin M. and Idaghdour, Youssef and Olby, Natasha J. and Munana, Karen R. and Gibson, Greg}, year={2009}, month={Dec}, pages={911–922} }
 @article{kennerly_ballmann_martin_wolfinger_gregory_stoskopf_gibson_2008, title={A gene expression signature of confinement in peripheral blood of red wolves (Canis rufus)}, volume={17}, ISSN={["1365-294X"]}, DOI={10.1111/j.1365-294X.2008.03775.x}, abstractNote={AbstractThe stresses that animals experience as a result of modification of their ecological circumstances induce physiological changes that leave a signature in profiles of gene expression. We illustrate this concept in a comparison of free range and confined North American red wolves (Canis rufus). Transcription profiling of peripheral blood samples from 13 red wolf individuals in the Alligator River region of North Carolina revealed a strong signal of differentiation. Four hundred eighty‐two out of 2980 transcripts detected on Illumina HumanRef8 oligonucleotide bead arrays were found to differentiate free range and confined wolves at a false discovery rate of 12.8% and P < 0.05. Over‐representation of genes in focal adhesion, insulin signalling, proteasomal, and tryptophan metabolism pathways suggests the activation of pro‐inflammatory and stress responses in confined animals. Consequently, characterization of differential transcript abundance in an accessible tissue such as peripheral blood identifies biomarkers that could be useful in animal management practices and for evaluating the impact of habitat changes on population health, particularly as attention turns to the impact of climate change on physiology and in turn species distributions.}, number={11}, journal={MOLECULAR ECOLOGY}, author={Kennerly, Erin and Ballmann, Anne and Martin, Stanton and Wolfinger, Russ and Gregory, Simon and Stoskopf, Michael and Gibson, Greg}, year={2008}, month={Jun}, pages={2782–2791} }
 @article{idaghdour_storey_jadallah_gibson_2008, title={A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan amazighs}, volume={4}, number={4}, journal={PLoS Genetics}, author={Idaghdour, Y. and Storey, J. D. and Jadallah, S. J. and Gibson, G.}, year={2008} }
 @article{need_attix_mcevoy_cirulli_linney_wagoner_gumbs_giegling_moeller_francks_et al._2008, title={Failure to replicate effect of Kibra on human memory in two large cohorts of European origin}, volume={147B}, ISSN={["1552-485X"]}, DOI={10.1002/ajmg.b.30658}, abstractNote={AbstractIt was recently suggested that the Kibra polymorphism rs17070145 has a strong effect on multiple episodic memory tasks in humans. We attempted to replicate this using two cohorts of European genetic origin (n = 319 and n = 365). We found no association with either the original SNP or a set of tagging SNPs in the Kibra gene with multiple verbal memory tasks, including one that was an exact replication (Auditory Verbal Learning Task, AVLT). These results suggest that Kibra does not have a strong and general effect on human memory. © 2008 Wiley‐Liss, Inc.}, number={5}, journal={AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS}, author={Need, Anna C. and Attix, Deborah K. and McEvoy, Jill M. and Cirulli, Elizabeth T. and Linney, Kristen N. and Wagoner, Ana Patricia and Gumbs, Curtis E. and Giegling, Ina and Moeller, Hans-Juergen and Francks, Clyde and et al.}, year={2008}, month={Jul}, pages={667–668} }
 @article{dworkin_kennerly_tack_hutchinson_brown_mahaffey_gibson_2009, title={Genomic Consequences of Background Effects on scalloped Mutant Expressivity in the Wing of Drosophila melanogaster}, volume={181}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.108.096453}, abstractNote={AbstractGenetic background effects contribute to the phenotypic consequences of mutations and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scallopedE3 (sdE3) mutation of Drosophila melanogaster is background dependent and is the result of at least one major modifier segregating between two standard lab wild-type strains. We provide evidence that at least one of the modifiers is linked to the vestigial region and demonstrate that the background effects modify the spatial distribution of known sd target genes in a genotype-dependent manner. In addition, microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large as or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sdE3 and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis and studies of epistasis and cryptic genetic variation segregating in natural populations.}, number={3}, journal={GENETICS}, author={Dworkin, Ian and Kennerly, Erin and Tack, David and Hutchinson, Jennifer and Brown, Julie and Mahaffey, James and Gibson, Greg}, year={2009}, month={Mar}, pages={1065–1076} }
 @misc{clark_eisen_smith_bergman_oliver_markow_kaufman_kellis_gelbart_iyer_et al._2007, title={Evolution of genes and genomes on the Drosophila phylogeny}, volume={450}, number={7167}, journal={Nature}, author={Clark, A. G. and Eisen, M. B. and Smith, D. R. and Bergman, C. M. and Oliver, B. and Markow, T. A. and Kaufman, T. C. and Kellis, M. and Gelbart, W. and Iyer, V. N. and et al.}, year={2007}, pages={203–218} }
 @article{gibson_2007, title={Human evolution: Thrifty genes and the dairy queen}, volume={17}, number={8}, journal={Current Biology}, author={Gibson, G.}, year={2007}, pages={R295–296} }
 @article{gibson_goldstein_2007, title={Human genetics: The hidden text of genome-wide associations}, volume={17}, number={21}, journal={Current Biology}, author={Gibson, G. and Goldstein, D. B.}, year={2007}, pages={R929–932} }
 @article{moser_carbone_arasu_gibson_2007, title={Impact of population structure on genetic diversity of a potential vaccine target in the canine hookworm (Ancylostoma caninum)}, volume={93}, ISSN={["1937-2345"]}, DOI={10.1645/GE-1096R.1}, abstractNote={Ancylostoma caninum is a globally distributed canine parasitic nematode. To test whether positive selection, population structure, or both affect genetic variation at the candidate vaccine target Ancylostoma secreted protein 1 (asp-1), we have quantified the genetic variation in A. caninum at asp-1 and a mitochondrial gene, cytochrome oxidase subunit 1 (cox-1), using the statistical population analysis tools found in the SNAP Workbench. The mitochondrial gene cox-1 exhibits moderate diversity within 2 North American samples, comparable to the level of variation observed in other parasitic nematodes. The protein coding portion for the C-terminal half of asp-1 shows similar levels of genetic variation in a Wake County, North Carolina, sample as cox-1. Standard tests of neutrality provide little formal evidence for selection acting on this locus, but haplotype networks for 2 of the exon regions have significantly different topologies, consistent with different evolutionary forces shaping variation at either end of a 1.3-kilobase stretch of sequence. Evidence for gene flow among geographically distinct samples suggests that the mobility of hosts of A. caninum is an important contributing factor to the population structure of the parasite.}, number={4}, journal={JOURNAL OF PARASITOLOGY}, author={Moser, Jennifer M. and Carbone, Ignazio and Arasu, Prema and Gibson, Greg}, year={2007}, month={Aug}, pages={796–805} }
 @article{hsieh_passador-gurgel_stone_gibson_2007, title={Mixture modeling of transcript abundance classes in natural populations}, volume={8}, ISSN={["1474-760X"]}, DOI={10.1186/gb-2007-8-6-r98}, abstractNote={Populations diverge in genotype and phenotype under the influence of such evolutionary processes as genetic drift, mutation accumulation, and natural selection. Because genotype maps onto phenotype by way of transcription, it is of interest to evaluate how these evolutionary factors influence the structure of variation at the level of transcription. Here, we explore the distributions of cis-acting and trans-acting factors and their relative contributions to expression of transcripts that exhibit two or more classes of abundance among individuals within populations. Expression profiling using cDNA microarrays was conducted in Drosophila melanogaster adult female heads for 58 nearly isogenic lines from a North Carolina population and 50 from a California population. Using a mixture modeling approach, transcripts were identified that exhibit more than one mode of transcript abundance across the samples. Power studies indicate that sample sizes of 50 individuals will generally be sufficient to detect divergent transcript abundance classes. The distribution of transcript abundance classes is skewed toward low frequency minor classes, which is reminiscent of the typical skew in genotype frequencies. Similar results are observed in reported data on gene expression in human lymphoblast cell lines, in which analysis of association with linked polymorphisms implies that cis-acting single nucleotide polymorphisms make only a modest contribution to bimodal distributions of transcript abundance. Population surveys of gene expression may complement genetical genomics as a general approach to quantifying sources of transcriptional variation. Differential expression of transcripts among individuals is due to a complex interplay of cis-acting and trans-acting factors.}, number={6}, journal={GENOME BIOLOGY}, author={Hsieh, Wen-Ping and Passador-Gurgel, Gisele and Stone, Eric A. and Gibson, Greg}, year={2007} }
 @article{passador-gurgel_hsieh_hunt_deighton_gibson_2007, title={Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster}, volume={39}, ISSN={["1061-4036"]}, DOI={10.1038/ng1944}, abstractNote={Although most genetic association studies are performed with the intention of detecting nucleotide polymorphisms that are correlated with a complex trait, transcript abundance should also be expected to associate with diseases or phenotypes. We performed a scan for such quantitative trait transcripts in adult female heads of the fruit fly (Drosophila melanogaster) that might explain variation for nicotine resistance. The strongest association was seen for abundance of ornithine aminotransferase transcripts, implicating detoxification and neurotransmitter biosynthesis as mediators of the quantitative response to the drug. Subsequently, genetic analysis and metabolite profiling confirmed a complex role for ornithine and GABA levels in modification of survival time upon chronic nicotine exposure. Differences between populations from North Carolina and California suggest that the resistance mechanism may be an evolved response to environmental exposure.}, number={2}, journal={NATURE GENETICS}, author={Passador-Gurgel, Gisele and Hsieh, Wen-Ping and Hunt, Priscilla and Deighton, Nigel and Gibson, Greg}, year={2007}, month={Feb}, pages={264–268} }
 @article{bushel_wolfinger_gibson_2007, title={Simultaneous clustering of gene expression data with clinical chemistry and pathological evaluations reveals phenotypic prototypes}, volume={1}, ISSN={["1752-0509"]}, DOI={10.1186/1752-0509-1-15}, abstractNote={Commonly employed clustering methods for analysis of gene expression data do not directly incorporate phenotypic data about the samples. Furthermore, clustering of samples with known phenotypes is typically performed in an informal fashion. The inability of clustering algorithms to incorporate biological data in the grouping process can limit proper interpretation of the data and its underlying biology. We present a more formal approach, the modk-prototypes algorithm, for clustering biological samples based on simultaneously considering microarray gene expression data and classes of known phenotypic variables such as clinical chemistry evaluations and histopathologic observations. The strategy involves constructing an objective function with the sum of the squared Euclidean distances for numeric microarray and clinical chemistry data and simple matching for histopathology categorical values in order to measure dissimilarity of the samples. Separate weighting terms are used for microarray, clinical chemistry and histopathology measurements to control the influence of each data domain on the clustering of the samples. The dynamic validity index for numeric data was modified with a category utility measure for determining the number of clusters in the data sets. A cluster's prototype, formed from the mean of the values for numeric features and the mode of the categorical values of all the samples in the group, is representative of the phenotype of the cluster members. The approach is shown to work well with a simulated mixed data set and two real data examples containing numeric and categorical data types. One from a heart disease study and another from acetaminophen (an analgesic) exposure in rat liver that causes centrilobular necrosis. The modk-prototypes algorithm partitioned the simulated data into clusters with samples in their respective class group and the heart disease samples into two groups (sick and buff denoting samples having pain type representative of angina and non-angina respectively) with an accuracy of 79%. This is on par with, or better than, the assignment accuracy of the heart disease samples by several well-known and successful clustering algorithms. Following modk-prototypes clustering of the acetaminophen-exposed samples, informative genes from the cluster prototypes were identified that are descriptive of, and phenotypically anchored to, levels of necrosis of the centrilobular region of the rat liver. The biological processes cell growth and/or maintenance, amine metabolism, and stress response were shown to discern between no and moderate levels of acetaminophen-induced centrilobular necrosis. The use of well-known and traditional measurements directly in the clustering provides some guarantee that the resulting clusters will be meaningfully interpretable.}, journal={BMC SYSTEMS BIOLOGY}, author={Bushel, Pierre R. and Wolfinger, Russell D. and Gibson, Greg}, year={2007}, month={Feb} }
 @misc{ayroles_gibson_2006, title={Analysis of variance of microarray data}, volume={411}, journal={Dna microarrays, part b: databases and statistics}, publisher={San Diego: Elsevier Academic Press Inc}, author={Ayroles, J. F. and Gibson, G.}, year={2006}, pages={214-} }
 @article{dworkin_gibson_2006, title={Epidermal growth factor receptor and transforming growth factor-beta signaling contributes to variation for wing shape in Drosophila melanogaster}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.053868}, abstractNote={Abstract
               Wing development in Drosophila is a common model system for the dissection of genetic networks and their roles during development. In particular, the RTK and TGF-β regulatory networks appear to be involved with numerous aspects of wing development, including patterning, cell determination, growth, proliferation, and survival in the developing imaginal wing disc. However, little is known as to how subtle changes in the function of these genes may contribute to quantitative variation for wing shape, per se. In this study 50 insertional mutations, representing 43 loci in the RTK, Hedgehog, TGF-β pathways, and their genetically interacting factors were used to study the role of these networks on wing shape. To concurrently examine how genetic background modulates the effects of the mutation, each insertion was introgressed into two wild-type genetic backgrounds. Using geometric morphometric methods, it is shown that the majority of these mutations have profound effects on shape but not size of the wing when measured as heterozygotes. To examine the relationships between how each mutation affects wing shape hierarchical clustering was used. Unlike previous observations of environmental canalization, these mutations did not generally increase within-line variation relative to their wild-type counterparts. These results provide an entry point into the genetics of wing shape and are discussed within the framework of the dissection of complex phenotypes.}, number={3}, journal={GENETICS}, author={Dworkin, Ian and Gibson, Greg}, year={2006}, month={Jul}, pages={1417–1431} }
 @article{gibson_2006, title={Evolution: The plastic transcriptorne}, volume={16}, number={8}, journal={Current Biology}, author={Gibson, G.}, year={2006}, pages={R285–287} }
 @article{moser_freitas_arasu_gibson_2005, title={Gene expression profiles associated with the transition to parasitism in Ancylostoma caninum larvae}, volume={143}, DOI={10.1016/j.molbiopran.2005.04.012}, number={1}, journal={Molecular and Biochemical Parasitology}, author={Moser, J. M. and Freitas, T. and Arasu, P. and Gibson, G.}, year={2005}, pages={39–48} }
 @article{goering_gibson_2005, title={Genetic variation for dorsal-ventral patterning of the Drosophila melanogaster eggshell}, volume={7}, ISSN={["1525-142X"]}, DOI={10.1111/j.1525-142X.2005.05009.x}, abstractNote={Summary
					 Patterning of the insect eggshell is an excellent system for exploring the molecular basis of phenotypic variation. In Drosophila melanogaster, two dorsal–anterior respiratory appendages are produced in response to signaling through the Epidermal growth factor receptor (Egfr). Previous work implicates Egfr pathway function in both intraspecific variation for dorsal appendage spacing (DAS) on the eggshell, as well as interspecific differences in dorsal appendage number and location. To test the hypothesis that genetic variation in Egfr contributes to variation in eggshell patterning, we have made use of naturally occurring intraspecific variation for DAS as a model quantitative trait. We found that there is substantial segregating genetic variation for DAS in D. melanogaster, and have tested for associations with 289 common polymorphisms in the Egfr locus. A marginal association was seen with two polymorphic sites in Egfr; however, we failed to replicate these findings in a second population, or in a modified quantitative complementation test designed to specifically test the effects of the putative polymorphisms. Therefore, we conclude that the polymorphisms we have identified in Egfr do not contribute to variation in DAS, and further work is required to understand the genetic architecture of this trait.}, number={2}, journal={EVOLUTION & DEVELOPMENT}, author={Goering, LM and Gibson, G}, year={2005}, pages={81–88} }
 @article{thomson_kennerly_olby_mickelson_hoffmann_dickinson_gibson_breen_2005, title={Microarray analysis of differentially expressed genes of primary tumors in the canine central nervous system}, volume={42}, ISSN={["1544-2217"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-24644472063&partnerID=MN8TOARS}, DOI={10.1354/vp.42-5-550}, abstractNote={ The pathophysiologic similarities of many human and canine cancers support the role of the domestic dog as a model for brain tumor research. Here we report the construction of a custom canine brain-specific cDNA microarray and the analysis of gene expression patterns of several different types of canine brain tumor The microarray contained 4000 clones from a canine brain specific cDNA library including 2161 clones that matched known genes or expressed sequence tags (ESTs) and 25 cancer-related genes. Our study included 16 brain tumors (seven meningiomas, five glial tumors, two ependymomas, and two choroid plexus papillomas) from a variety of different dog breeds. We identified several genes previously found to be differentially expressed in human brain tumors. This suggests that human and canine brain tumors share a common pathogenesis. In addition, we also found differentially expressed genes unique to either meningiomas or the glial tumors. This report represents the first global gene expression analysis of different types of canine brain tumors by cDNA microarrays and might aid in the identification of potential candidate genes involved in tumor formation and progression. }, number={5}, journal={VETERINARY PATHOLOGY}, author={Thomson, SAM and Kennerly, E and Olby, N and Mickelson, JR and Hoffmann, DE and Dickinson, PJ and Gibson, G and Breen, M}, year={2005}, month={Sep}, pages={550–558} }
 @article{gibson_2005, title={Mutation accumulation of the transcriptome}, volume={37}, number={5}, journal={Nature Genetics}, author={Gibson, G.}, year={2005}, pages={458–460} }
 @article{gibson_2005, title={Q & A - Greg Gibson}, volume={15}, ISSN={["0960-9822"]}, DOI={10.1016/j.cub.2005.07.016}, abstractNote={Greg Gibson grew up in Canberra, Australia, and did his undergraduate degree in Biology at the University of Sydney. He moved to Basel, Switzerland, for his PhD on the specificity of homeotic genes in Drosophila, and then to Stanford for post-doctoral research, where his interests turned to the quantitative genetics of development in flies. After a year at Duke University he took up a junior faculty position at the University of Michigan, where he received a David and Lucille Packard Foundation fellowship that was the key to establishing his research program. He moved to the Genetics Department at North Carolina State University, also as an Assistant Professor, in 1998, where he adopted genomics approaches to quantitative evolutionary genetics. Together with Spencer Muse, he wrote ‘A Primer of Genome Science’, published by Sinauer Associates, now in its second edition. He is currently conducting research on association studies and quantitative transcription profiling in relation to morphogenesis and physiology on Drosophila, with a growing interested in canine genomics as well. How did you become interested in genetics? Well, both of my parents were biologists, so naturally I didn’t want to have anything to do with biology in high school. At Sydney Uni, I was studying science and law together, struggling with the mendacity of torts. My father gave me a book on genetics to read. By the time I finished chapter 3 I’d decided to make solving the genetic code my life’s work; then I discovered in chapter 5 that the problem was solved. But I was hooked. If not the genetic code, then what hooked you? Pattern formation. The next year we were introduced to transdetermination — the change in fate of Drosophila imaginal discs from, say, antenna to leg, when you culture them for a long time in larvae. Walter Gehring, who did much of that work, happened to be on a tour of Australia, just at the time his lab was cloning the Drosophila Antennapedia complex. This complex encodes a series of genes that, when mutated, change antenna into leg, for example. He gave a seminar on the homeobox, and it was just amazing to learn that this little bit of a gene holds a key to the evolution and development of the body plan. The next thing you know I was on the plane to Switzerland for a PhD. Who else have been your greatest influences? I’ve been very lucky to have been mentored by a series of extraordinary scientists, who approached science very differently but all respected the essential need for individual exploration. At a critical juncture as a post-doc, while I was deciding, without really realizing it, to switch from developmental to quantitative genetics, I went to a workshop at Stanford. One senior geneticist told me straight up that I was naïve and misguided. Technically he was right, but luckily Andy Clark was also there and he immediately offered support and encouragement. One chance encounter can change the course of a career. What advice would you give young scientists? Be passionate, find your niche, and let the environment around you make you better. I think it is important to work with someone whose work inspires you, but most of the time you are going to be learning more from all of the other colleagues and peers around you. The other important thing is to be open-minded to diverse approaches. For example, coming to North Carolina State University was novel for me, because there is definitely a different atmosphere in land grant universities. After a while, I realized that people working on pigs and maize are asking basically the same questions as Drosophilists and Arabidopsans. Genomics enables us all to talk together now, so there is great potential for cross-fertilization. Hence your new interest in canine genomics? Yes, dogs are obviously a wonderful system for studying developmental and behavioral evolution, but they are also emerging as a very useful model for toxicology and parasitology. For example, one quarter of the world’s population is infected with intestinal hookworms that contribute to enormous loss of human potential, yet they receive little attention, so we have done some work on canine hookworm as a model. What are the big questions all biologists are asking, then? I’m not so sure if we’re really asking them! I guess consciousness and the origin of biological complexity are two areas where we are pretty much clueless. The latter is closest to my research interests: I’m probably best known for my work on canalization, which is the evolution of the buffering of development. When you perturb genetic systems, you don’t just change the mean value of a trait, you also usually increase its variability. I suspect this phenomenon has something to do with the epidemic nature of what we tend to think of as genetic diseases, like diabetes, depression and asthma. In the modern environment we may just be exposing much more ‘cryptic’ genetic variation. Solving this riddle also has implications for understanding how novel biochemical, physiological and developmental genetic networks arise and evolve. These are all genetic questions, what about other sciences? Actually, I think our biggest issues are educational and cultural. If biology is going to be the science of the 21st century, we really have to pay attention to the social upheaval this is feeding. I think people are afraid of genetics at some level, because they do not understand it and it butts up against beliefs and value systems (which is something that I do not understand). Biologists and theologians are going to have to work together to counterbalance the extreme fundamentalist attitudes that threaten pluralism and rationalism. Are you saying that religion is also something that geneticists should be studying? No, not at all. Every individual has to find their own accommodation between their spirituality and their scientific knowledge. For me personally, there is no need for a god, and a secular world view is much richer and more hopeful, but obviously there are millions of Christians and Jews and Hindus and others who have no problem integrating faith into their scientific worldview. The tragedy is that there is a strong echo-chamber out there that equates ‘belief’ in evolution with immorality. I suspect we have ourselves partly to blame, arrogantly proclaiming threatening ideas from selfish genes through sociobiology to social Darwinism as if they are some higher truth. What is the educational challenge then? To help people to understand genetics, which like it or not is going to play a bigger and bigger role in everyone’s lives, without being threatened. Approaching half of all American college students, including probably over a quarter of all biology majors, now regard intelligent design and evolution as equally valid explanations for the origin of life on Earth. Another quarter reject evolution altogether. That isn’t a problem in itself, except that it tends to come with a whole package of anti-intellectual stuff. If the fraction approaches fifty percent, I worry that we will enter a social phase transition that starts to reject rational enquiry itself. I guess we need to stop casting evolution in opposition to religion, and start seeing these as two arms of the quest to understand human nature, working together and building on a common tradition of enquiry.}, number={14}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={2005}, month={Jul}, pages={R531–R532} }
 @article{dworkin_palsson_gibson_2005, title={Replication of an egfr-wing shape association in a wild-caught cohort of Drosaphila melanogaster}, volume={169}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.035766}, abstractNote={Abstract
               Linkage disequilibrium mapping has been used extensively in medical and evolutionary genetics to map causal polymorphisms within genes associated with disease status or phenotypic variation for a trait. However, the initial findings of most nonhuman studies have not been replicated in subsequent studies, due in part to false positives, as well as additional factors that can render true positives unreplicable. These factors may be more severe when the initial study is performed using an experimental population of organisms reared under controlled lab conditions. We demonstrate that despite considerable phenotypic differences for wing shape between a lab-reared experimental population and a wild-caught cohort of Drosophila melanogaster, an association between a putative regulatory polymorphism in Egfr and wing shape can be replicated. These results are discussed both within the framework of future association-mapping studies and within the context of the evolutionary dynamics of alleles in populations.}, number={4}, journal={GENETICS}, author={Dworkin, I and Palsson, A and Gibson, G}, year={2005}, month={Apr}, pages={2115–2125} }
 @misc{gibson_2005, title={Robustness and evolvability in living systems}, volume={310}, number={5746}, journal={Science}, author={Gibson, G.}, year={2005}, pages={237} }
 @article{palsson_dodgson_dworkin_gibson_2005, title={Tests for the replication of an association between Egfr and natural variation in Drosophila melanogaster wing morphology}, volume={6}, journal={BMC Genetics}, author={Palsson, A. and Dodgson, J. and Dworkin, I. and Gibson, G.}, year={2005} }
 @misc{gibson_weir_2005, title={The quantitative genetics of transcription}, volume={21}, ISSN={["0168-9525"]}, DOI={10.1016/j.tig.2005.08.010}, abstractNote={Quantitative geneticists have become interested in the heritability of transcription and detection of expression quantitative trait loci (eQTLs). Linkage mapping methods have identified major-effect eQTLs for some transcripts and have shown that regulatory polymorphisms in cis and in trans affect expression. It is also clear that these mapping strategies have little power to detect polygenic factors, and some new statistical approaches are emerging that paint a more complex picture of transcriptional heritability. Several studies imply pervasive non-additivity of transcription, transgressive segregation and epistasis, and future studies will soon document the extent of genotype–environment interaction and population structure at the transcriptional level. The implications of these findings for genotype–phenotype mapping and modeling the evolution of transcription are discussed. Quantitative geneticists have become interested in the heritability of transcription and detection of expression quantitative trait loci (eQTLs). Linkage mapping methods have identified major-effect eQTLs for some transcripts and have shown that regulatory polymorphisms in cis and in trans affect expression. It is also clear that these mapping strategies have little power to detect polygenic factors, and some new statistical approaches are emerging that paint a more complex picture of transcriptional heritability. Several studies imply pervasive non-additivity of transcription, transgressive segregation and epistasis, and future studies will soon document the extent of genotype–environment interaction and population structure at the transcriptional level. The implications of these findings for genotype–phenotype mapping and modeling the evolution of transcription are discussed.}, number={11}, journal={TRENDS IN GENETICS}, author={Gibson, G and Weir, B}, year={2005}, month={Nov}, pages={616–623} }
 @article{gibson_2005, title={The synthesis and evolution of a supermodel}, volume={307}, ISSN={["0036-8075"]}, DOI={10.1126/science.1109835}, abstractNote={Threespine stickleback populations in freshwater habitats show many differences in morphology and behavior relative to their marine ancestors. A common morphological difference seen in the freshwater stickleback variants is the loss of armor plates found in marine species. In his Perspective,
 Gibson
 discusses the discovery that repeated selection of
 Eda
 alleles (encoding the protein ectodysplasin) resulted in the parallel evolution of the low-armor stickleback forms in most freshwater locations (
 Colosimo
 et al.).}, number={5717}, journal={SCIENCE}, author={Gibson, G}, year={2005}, month={Mar}, pages={1890–1891} }
 @book{gibson_muse_2004, title={A primer of genome science (2nd ed.)}, ISBN={0878932321}, publisher={Sunderland, MA: Sinauer Associates}, author={Gibson, G. and Muse, S. V.}, year={2004} }
 @article{ranz_namgyal_gibson_hartl_2004, title={Anomalies in the expression profile of interspecific hybrids of Drosophila melanogaster and Drosophila simulans}, volume={14}, ISSN={["1549-5469"]}, DOI={10.1101/gr.2019804}, abstractNote={When females of Drosophila melanogaster and males of Drosophila simulans are mated, the male progeny are inviable, whereas the female progeny display manifold malformations and are sterile. These abnormalities result from genetic incompatibilities accumulated since the time the lineages of the species diverged, and may have their origin in aberrant gene transcription. Because compensatory changes within species may obscure differences at the regulatory level in conventional comparisons of the expression profile between species, we have compared the gene-expression profile of hybrid females with those of females of the parental species in order to identify regulatory incompatibilities. In the hybrid females, we find abnormal levels of messenger RNA for a large fraction of the Drosophila transcriptome. These include a gross underexpression of genes preferentially expressed in females, accompanying gonadal atrophy. The hybrid females also show significant overexpression of male-biased genes, which we attribute to incompatibilities in the regulatory mechanisms that normally act to control the expression of these genes in females. The net result of the multiple incompatibilities is that the gene-expression profiles of the parental females are more similar to each other than either is to that of the hybrid.}, number={3}, journal={GENOME RESEARCH}, author={Ranz, JM and Namgyal, K and Gibson, G and Hartl, DL}, year={2004}, month={Mar}, pages={373–379} }
 @article{palsson_gibson_2004, title={Association between nudeotide variation in Egfr and wing shape in Drosophild melanogaster}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.103.021766}, abstractNote={Abstract
               As part of an effort to dissect quantitative trait locus effects to the nucleotide level, association was assessed between 238 single-nucleotide and 20 indel polymorphisms spread over 11 kb of the Drosophila melanogaster Egfr locus and nine relative warp measures of wing shape. One SNP in a conserved potential regulatory site for a GAGA factor in the promoter of alternate first exon 2 approaches conservative experimentwise significance (P < 0.00003) in the sample of 207 lines for association with the location of the crossveins in the central region of the wing. Several other sites indicate marginal association with one or more other aspects of shape. No strong effects of sex or population of origin were detected with measures of shape, but two different sites were strongly associated with overall wing size in interaction with these fixed factors. Whole-gene sequencing in very large samples, rather than selective genotyping, would appear to be the only strategy likely to be successful for detecting subtle associations in species with high polymorphism and little haplotype structure. However, these features severely limit the ability of linkage disequilibrium mapping in Drosophila to resolve quantitative effects to single nucleotides.}, number={3}, journal={GENETICS}, author={Palsson, A and Gibson, G}, year={2004}, month={Jul}, pages={1187–1198} }
 @article{zhou_gibson_2004, title={Cross-species comparison of genome-wide expression patterns}, volume={5}, number={7}, journal={Genome Biology}, author={Zhou, X. H. J. and Gibson, G.}, year={2004} }
 @article{nikoh_duty_gibson_2004, title={Effects of population structure and sex on association between serotonin receptors and Drosophila heart rate}, volume={168}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.028712}, abstractNote={Abstract
               As a first step toward population and quantitative genetic analysis of neurotransmitter receptors in Drosophila melanogaster, we describe the parameters of nucleotide variation in three serotonin receptors and their association with pupal heart rate. Thirteen kilobases of DNA including the complete coding regions of 5-HT1A, 5-HT1B, and 5-HT2 were sequenced in 216 highly inbred lines extracted from two North American populations in California and North Carolina. Nucleotide and amino acid polymorphism is in the normal range for Drosophila genes and proteins, and linkage disequilibrium decays rapidly such that haplotype blocks are typically only a few SNPs long. However, intron 1 of 5-HT1A consists of two haplotypes that are at significantly different frequencies in the two populations. Neither this region of the gene nor any of the common amino acid polymorphisms in the three loci associate with either heart rate or heart rate variability. A cluster of SNPs in intron 2 of 5-HT1A, including a triallelic site, do show a highly significant interaction between genotype, sex, and population. While it is likely that a combination of weak, complex selection pressures and population structure has helped shape variation in the serotonin receptors of Drosophila, much larger sampling strategies than are currently adopted in evolutionary genetics will be required to disentangle these effects.}, number={4}, journal={GENETICS}, author={Nikoh, N and Duty, A and Gibson, G}, year={2004}, month={Dec}, pages={1963–1974} }
 @article{gibson_riley-berger_harshman_kopp_vacha_nuzhdin_wayne_2004, title={Extensive sex-specific nonadditivity of gene expression in Drosophila melanogaster}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.026583}, abstractNote={Abstract
               Assessment of the degree to which gene expression is additive and heritable has important implications for understanding the maintenance of variation, adaptation, phenotypic divergence, and the mapping of genotype onto phenotype. We used whole-genome transcript profiling using Agilent long-oligonucleotide microarrays representing 12,017 genes to demonstrate that gene transcription is pervasively nonadditive in Drosophila melanogaster. Comparison of adults of two isogenic lines and their reciprocal F1 hybrids revealed 5820 genes as significantly different between at least two of the four genotypes in either males or females or across both sexes. Strikingly, while 25% of all genes differ between the two parents, 33% differ between both F1's and the parents, averaged across sexes. However, only 5% of genes show overdominance, suggesting that heterosis for expression is rare.}, number={4}, journal={GENETICS}, author={Gibson, G and Riley-Berger, R and Harshman, L and Kopp, A and Vacha, S and Nuzhdin, S and Wayne, M}, year={2004}, month={Aug}, pages={1791–1799} }
 @article{mcgraw_gibson_clark_wolfner_2004, title={Genes Regulated by Mating, Sperm, or Seminal Proteins in Mated Female Drosophila melanogaster}, volume={14}, ISSN={0960-9822}, url={http://dx.doi.org/10.1016/j.cub.2004.08.028}, DOI={10.1016/j.cub.2004.08.028}, abstractNote={In Drosophila melanogaster, sperm and accessory gland proteins (“Acps,” a major component of seminal fluid) transferred by males during mating trigger many physiological and behavioral changes in females (reviewed in [1Kubli E. Sex-peptides seminal peptides of the Drosophila male.Cell. Mol. Life Sci. 2003; 60: 1689-1704Crossref PubMed Scopus (228) Google Scholar, 2Wolfner M.F. The gifts that keep on giving physiological functions and evolutionary dynamics of male seminal proteins in Drosophila.Heredity. 2002; 88: 85-93Crossref PubMed Scopus (353) Google Scholar, 3Swanson W.J. Vacquier V.D. The rapid evolution of reproductive proteins.Nat. Rev. Genet. 2002; 3: 137-144Crossref PubMed Scopus (958) Google Scholar, 4Chapman T. Seminal fluid-mediated fitness traits in Drosophila.Heredity. 2001; 87: 511-521Crossref PubMed Scopus (324) Google Scholar, 5Gillott C. Male accessory gland secretions modulators of female reproductive physiology and behavior.Annu. Rev. Entomol. 2003; 48: 163-184Crossref PubMed Scopus (589) Google Scholar]). Determining the genetic changes triggered in females by male-derived molecules and cells is a crucial first step in understanding female responses to mating and the female's role in postcopulatory processes such as sperm competition, cryptic female choice, and sexually antagonistic coevolution. We used oligonucleotide microarrays to compare gene expression in D. melanogaster females that were either virgin, mated to normal males, mated to males lacking sperm, or mated to males lacking both sperm and Acps. Expression of up to 1783 genes changed as a result of mating, most less than 2-fold. Of these, 549 genes were regulated by the receipt of sperm and 160 as a result of Acps that females received from their mates. The remaining genes whose expression levels changed were modulated by nonsperm/non-Acp aspects of mating. The mating-dependent genes that we have identified contribute to many biological processes including metabolism, immune defense, and protein modification.}, number={16}, journal={Current Biology}, publisher={Elsevier BV}, author={McGraw, Lisa A. and Gibson, Greg and Clark, Andrew G. and Wolfner, Mariana F.}, year={2004}, month={Aug}, pages={1509–1514} }
 @article{palsson_rouse_riley-berger_dworkin_gibson_2004, title={Nucleotide variation in the Egfr locus of Drosophila melanogaster}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.026252}, abstractNote={Abstract
               The Epidermal growth factor receptor is an essential gene with diverse pleiotropic roles in development throughout the animal kingdom. Analysis of sequence diversity in 10.9 kb covering the complete coding region and 6.4 kb of potential regulatory regions in a sample of 250 alleles from three populations of Drosophila melanogaster suggests that the intensity of different population genetic forces varies along the locus. A total of 238 independent common SNPs and 20 indel polymorphisms were detected, with just six common replacements affecting >1475 amino acids, four of which are in the short alternate first exon. Sequence diversity is lowest in a 2-kb portion of intron 2, which is also highly conserved in comparison with D. simulans and D. pseudoobscura. Linkage disequilibrium decays to background levels within 500 bp of most sites, so haplotypes are generally restricted to up to 5 polymorphisms. The two North American samples from North Carolina and California have diverged in allele frequency at a handful of individual SNPs, but a Kenyan sample is both more divergent and more polymorphic. The effect of sample size on inference of the roles of population structure, uneven recombination, and weak selection in patterning nucleotide variation in the locus is discussed.}, number={3}, journal={GENETICS}, author={Palsson, A and Rouse, A and Riley-Berger, R and Dworkin, I and Gibson, G}, year={2004}, month={Jul}, pages={1199–1212} }
 @misc{gibson_dworkin_2004, title={Uncovering cryptic genetic variation}, volume={5}, ISSN={["1471-0064"]}, DOI={10.1038/nrg1426}, abstractNote={Cryptic genetic variation is the dark matter of biology: it is variation that is not normally seen, but that might be an essential source of physiological and evolutionary potential. It is uncovered by environmental or genetic perturbations, and is thought to modify the penetrance of common diseases, the response of livestock and crops to artificial selection and the capacity of populations to respond to the emergence of a potentially advantageous macro-mutation. We argue in this review that cryptic genetic variation is pervasive but under-appreciated, we highlight recent progress in determining the nature and identity of genes that underlie cryptic genetic effects and we outline future research directions.}, number={9}, journal={NATURE REVIEWS GENETICS}, author={Gibson, G and Dworkin, I}, year={2004}, month={Sep}, pages={681–U11} }
 @article{honeycutt_gibson_2004, title={Use of regression methods to identify motifs that modulate germline transcription in Drosophila melanogaster}, volume={83}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672304006780}, abstractNote={Identification of cis-regulatory motifs has been difficult due to the short and variable length of the sequences that bind transcription factors. Using both sequence and microarray expression data, we present a method for identifying cis-regulatory motifs that uses regression trees to refine results from simple linear regression of expression levels on motif counts. Analysis of expression patterns from two separate datasets for genes showing significant differences in expression between the sexes in Drosophila melanogaster resulted in a model that identified known binding sites upstream of genes that are differentially expressed in the germline. We obtained a strong result for motif TCGATA, part of the larger, characterized binding site of dGATAb protein. We also identified an uncharacterized motif that is positively associated with sex-biased expression and was assembled from smaller motifs grouped by our model. A regression tree model provides a grouping of independent variables into multiple linear models, an advantage over a single multivariate model. In our case, this grouping of motifs suggests binding sites for cooperating factors in sex-specific expression, as well as a way of combining smaller motifs into larger binding sites.}, number={3}, journal={GENETICS RESEARCH}, author={Honeycutt, E and Gibson, G}, year={2004}, month={Jun}, pages={177–188} }
 @article{riley_jin_gibson_2003, title={Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila}, volume={12}, ISSN={["1365-294X"]}, DOI={10.1046/j.1365-294X.2003.01741.x}, abstractNote={AbstractThe molecular genetics of several signal transduction pathways is well characterized, providing an opportunity to address the nature of the population genetic forces acting on functionally related suites of pleiotropic regulatory genes. Signal transduction is the process by which signals are transmitted from the cell surface to the nucleus or other cellular structures. It plays a fundamental role in regulating a wide range of developmental and physiological processes, many of which are likely to be subject to buffering mechanisms. Here we infer that contrasting selection pressures act on six components of the Ras signal transduction pathway by comparing sequences obtained from 25 alleles of Drosophila melanogaster with one allele of the sibling species D. simulans. The three most upstream components of the cascade, Ras, Drk and polehole, experience strong purifying selection, as they show no fixed amino acid differences between the species and just a handful of rare replacement polymorphisms within D. melanogaster. This portion of the pathway is likely to act as a control point in signal transduction, because the more downstream components Dsor1, corkscrew and Ksr, each show several amino acid replacements between the species. Furthermore, Ksr is nearly monomorphic within D. melanogaster, and application of the HKA and McDonald and Kreitman tests indicate that this gene may have experienced a recent selective sweep, suggesting that modifiers of Ras kinase signalling are the most likely source of quantitative variation associated with this core regulatory pathway.}, number={5}, journal={MOLECULAR ECOLOGY}, author={Riley, RM and Jin, W and Gibson, G}, year={2003}, month={May}, pages={1315–1323} }
 @article{dworkin_palsson_birdsall_gibson_2003, title={Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster}, volume={13}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2003.10.001}, abstractNote={One objective of quantitative genetics is to identify the nucleotide variants within genes that contribute to phenotypic variation and susceptibility [1Stern D.L. Perspective evolutionary developmental biology and the problem of variation.Evolution. 2000; 54: 1079-1091PubMed Google Scholar]. In an evolutionary context, this means characterizing the molecular polymorphisms that modify the penetrance and expressivity of perturbed traits. A survey of association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the degree of eye roughening due to a gain-of-function EgfrE1 allele crossed into 210 isogenic wild-type lines provides evidence that a handful of synonymous substitutions supply cryptic variation for photoreceptor determination. Ten sites exceed Bonferroni threshold for association in two sets of crosses to different EgfrE1 backgrounds including a particularly significant cluster of sites in tight linkage disequilibrium toward the 3′ end of the coding region. Epistatic interaction of this cluster with one other site enhances the expressivity of this haplotype. Replication of the strongest associations with an independent sample of 302 phenotypically extreme individuals derived from 1000 crosses of EgfrE1 to freshly trapped males was achieved using modified case-control and transmission-disequilibrium tests. A tendency for the rarer alleles to have more disrupted eye development suggests that mutation-selection balance is a possible mechanism contributing to maintaining cryptic variation for Egfr.}, number={21}, journal={CURRENT BIOLOGY}, author={Dworkin, I and Palsson, A and Birdsall, K and Gibson, G}, year={2003}, month={Oct}, pages={1888–1893} }
 @article{purugganan_gibson_2003, title={Merging ecology, molecular evolution, and functional genetics}, volume={12}, ISSN={["0962-1083"]}, DOI={10.1046/j.1365-294X.2003.01851.x}, abstractNote={'This structure has novel features which are of considerable biological interest.' This has to be one of the boldest understatements in all of biology, written 50 years ago in Nature by Francis Crick and Jim Watson in describing their model for the DNA double helix (Watson & Crick 1953). The unveiling of the structure of the molecule that carries the hereditary information of living organisms is rightly hailed as a landmark in the history of science, and we rightly celebrate the golden anniversary of this discovery this year. Understanding the molecular basis of genes has transformed biological research since 1953, and ecologists have participated in the fruits of this revolution. The use of molecular markers, beginning with restriction fragment length polymorphisms (RFLPs) to today's single nucleotide polymorphisms (SNPs), has had a significant impact on our ability to trace parentage and kinship, to measure gene flow and migration patterns and to reconstruct the demographic histories of populations and species. Few will argue that the advent of modern genetic technology has provided an unparalleled ability to examine evolutionary and ecological forces in nature. Yet the full impact of molecular genetics (and today, genomics) has yet to be felt by the discipline of ecology. While the use of molecular markers by ecologists has been fruitful, there is more to the molecules than their current dominant role in ecological research as mere genetic barcodes. We have yet to understand ecological processes at a fundamentally molecular level, and our inability to make this connection from the ecological gene to the ecological organism hampers any dreams we may harbour of creating a unified picture of life. We do not know, to a large extent, the interplay between genes and the ecological processes that dominate life at and above the organ-ismal level. We stand today at a crossroads that provide unprecedented opportunity to make these connections. Molecular biologists have proved adept at unravelling the molecular mechanisms behind many of the physiological, developmental and at times behavioural processes that characterize organismal lives. It is time that ecologists make use of this information in meaningful ways to gain further insights into the nature of organismal ecologies. How do we go about doing this? There is no one single answer to this question. There remains no single coherent program of molecular ecology. But it is the diversity of approaches that make this an interesting enterprise, and in this issue we …}, number={5}, journal={MOLECULAR ECOLOGY}, author={Purugganan, M and Gibson, G}, year={2003}, month={May}, pages={1109–1112} }
 @article{gibson_2003, title={Microarray analysis - Genome-scale hypothesis scanning}, volume={1}, ISSN={["1544-9173"]}, DOI={10.1371/journal.pbio.0000015}, abstractNote={Microarrays can survey genome-wide expression patterns. Not only can these gene expression profiles be used to identify a few genes of interest, they are now being creatively applied for hypothesis generation and testing}, number={1}, journal={PLOS BIOLOGY}, author={Gibson, G}, year={2003}, month={Oct}, pages={28–29} }
 @article{hsieh_chu_wolfinger_gibson_2003, title={Mixed-model reanalysis of primate data suggests tissue and species biases in oligonucleotide-based gene expression profiles}, volume={165}, number={2}, journal={Genetics}, author={Hsieh, W. P. and Chu, T. M. and Wolfinger, R. D. and Gibson, G.}, year={2003}, pages={747–757} }
 @article{visser_hermisson_wagner_meyers_bagheri_blanchard_chao_cheverud_elena_fontana_et al._2003, title={Perspective: Evolution and detection of genetic robustness}, volume={57}, ISSN={["1558-5646"]}, DOI={10.1554/02-750R}, abstractNote={Abstract Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness—genetic robustness—and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness; and (3) exploring the implications of genetic robustness for future evolution.}, number={9}, journal={EVOLUTION}, author={Visser, JAGM and Hermisson, J and Wagner, GP and Meyers, LA and Bagheri, HC and Blanchard, JL and Chao, L and Cheverud, JM and Elena, SF and Fontana, W and et al.}, year={2003}, month={Sep}, pages={1959–1972} }
 @article{gibson_2003, title={Population genomics: Finding the dispatch variants of mass disruption}, volume={13}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2003.11.008}, abstractNote={A study of positive selection on the promoter of the human interleukin-4 gene suggests that some disease-promoting alleles might be identified as polymorphic sites that affect transcription and occur at different frequencies among human populations.}, number={23}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={2003}, month={Dec}, pages={R901–R903} }
 @article{gibson_2003, title={Population genomics: celebrating individual expression}, volume={90}, ISSN={["0018-067X"]}, DOI={10.1038/sj.hdy.6800195}, abstractNote={Future efforts to map genotype onto phenotype may well use gene expression profiling alongside scanning for association between genetic variants and traits. The basic idea is similar, but the difference is that we will look for transcripts rather than SNPs that are correlated with a phenotype. In fact, microarray analysis offers a couple of advantages for quantitative genetic analysis. One is that it is efficient and comprehensive, so true genome-wide scans can be envisaged for a wide variety of organisms. The other is that transcript abundance already integrates developmental and environmental noise with regulatory polymorphisms. Thus, we might expect variation in transcript abundance to be somewhat closer to phenotypic variation than are the actual genotypes.}, number={1}, journal={HEREDITY}, author={Gibson, G}, year={2003}, month={Jan}, pages={1–2} }
 @article{gibson_2002, title={A genetic attack on the defense complex}, volume={24}, ISSN={["1521-1878"]}, DOI={10.1002/bies.10104}, abstractNote={AbstractAn increasing number of “non‐model” organisms are becoming accessible to genetic analysis in the field, as evolutionary biologists develop dense molecular genetic maps. Peichel et al.'s recent study1 provides a microsatellite‐based map for threespine stickleback fish (Gasterosteus aculeatus), and the first evidence for QTL affecting feeding morphology and defensive armor. This species has undergone rapid and parallel morphological and behavioral evolution, and there is now hope that some of the genes responsible for the divergence may soon be identified. BioEssays 24:487–489, 2002. © 2002 Wiley Periodicals, Inc.}, number={6}, journal={BIOESSAYS}, author={Gibson, G}, year={2002}, month={Jun}, pages={487–489} }
 @book{gibson_muse_2002, title={A primer of genome science}, ISBN={0878932348}, publisher={Sunderland, MA: Sinauer}, author={Gibson, G. and Muse, S. V.}, year={2002} }
 @article{gibson_2002, title={Developmental evolution: Getting robust about robustness}, volume={12}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(02)00855-2}, abstractNote={In the context of development, a process is robust if it can proceed normally despite the enormous capacity for perturbation inherent in all biological systems. A new mode of theoretical modeling of genetic networks holds great promise for increasing our understanding of both the quantitative mechanisms of robustness and its evolutionary impact.}, number={10}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={2002}, month={May}, pages={R347–R349} }
 @misc{gibson_mackay_2002, title={Enabling population and quantitative genomics}, volume={80}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672302005839}, abstractNote={Dissection of quantitative traits to the nucleotide level requires phenotypic and genotypic analysis of traits on a genome scale. Here we discuss the set of community-wide genetic and molecular resources, including panels of specific types of inbred lines and high density resequencing and SNP detection, that will facilitate such studies.}, number={1}, journal={GENETICS RESEARCH}, author={Gibson, G and Mackay, TFC}, year={2002}, month={Aug}, pages={1–6} }
 @article{gibson_2002, title={Microarrays in ecology and evolution: A preview.}, volume={11}, number={1}, journal={Molecular Ecology}, author={Gibson, G.}, year={2002}, pages={17–24} }
 @misc{gibson_2002, title={Microarrays in ecology and evolution: a preview}, volume={11}, ISSN={["1365-294X"]}, DOI={10.1046/j.0962-1083.2001.01425.x}, abstractNote={AbstractMicroarray technology provides a new tool with which molecular ecologists and evolutionary biologists can survey genome‐wide patterns of gene expression within and among species. New analytical approaches based on analysis of variance will allow quantification of the contributions of among individual variation, genotype, sex, microenvironment, population structure, and geography to variation in gene expression. Applications of this methodology are reviewed in relation to studies of mechanisms of adaptation and divergence; delineation of developmental and physiological pathways and networks; characterization of quantitative genetic parameters at the level of transcription (‘quantitative genomics’); molecular dissection of parasitism and symbiosis; and studies of the diversification of gene content. Establishment of microarray resources is neither prohibitively expensive nor technologically demanding, and a commitment to development of gene expression profiling methods for nonmodel organisms could have a tremendous impact on molecular and genetic research at the interface of organismal and population biology.}, number={1}, journal={MOLECULAR ECOLOGY}, author={Gibson, G}, year={2002}, month={Jan}, pages={17–24} }
 @article{gibson_honeycutt_2002, title={The evolution of developmental regulatory pathways}, volume={12}, ISSN={["1879-0380"]}, DOI={10.1016/S0959-437X(02)00352-0}, abstractNote={Evolutionary analysis of the content of developmental regulatory pathways has been advanced by the publication of pairs of complete genome sequences from representative taxonomic groups. Annotation of the fission yeast, rice, and mouse genomes confirms that most regulatory families are shared among eukaryotes but also shows that certain gene families have restricted distributions. Theoretical advances in the past few years include development of the theory of scale-free networks, which provides a new framework in which to consider the connectivity and evolution of regulatory systems, and introduction of algorithms that use comparative data to enhance detection of transcriptional regulatory motifs.}, number={6}, journal={CURRENT OPINION IN GENETICS & DEVELOPMENT}, author={Gibson, G and Honeycutt, E}, year={2002}, month={Dec}, pages={695–700} }
 @article{carrillo_gibson_2002, title={Unusual genetic architecture of natural variation affecting drug resistance in Drosophila melanogaster}, volume={80}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672302005888}, abstractNote={Naturally occurring genetic variation was quantified for survival time of adult Drosophila melanogaster exposed to chronic ingestion of the drugs nicotine, caffeine, dopamine, tyramine and octopamine. Responses to nicotine, tyramine and octopamine were genetically correlated in both sexes, whereas caffeine response correlated with starvation resistance. However, there is also genetic variation that is specific for each of the drugs. Females tended to be more resistant than males to nicotine and caffeine but sex-by-genotype interactions were also seen for these drugs and for the response to dopamine. An unusual and complex genetic architecture was observed in crosses between lines with different responses to caffeine ingestion. Additive and dominance components were clearly seen from the analysis of F1 individuals, but increased female resistance to caffeine in backcross generations and increased male sensitivity in F2 generations confused the interpretation of possible epistatic contributions.}, number={3}, journal={GENETICAL RESEARCH}, author={Carrillo, R and Gibson, G}, year={2002}, month={Dec}, pages={205–213} }
 @article{wolfinger_gibson_wolfinger_bennett_hamadeh_bushel_afshari_paules_2001, title={Assessing gene significance from cDNA microarray expression data via mixed models}, volume={8}, ISSN={["1066-5277"]}, url={https://doi.org/10.1089/106652701753307520}, DOI={10.1089/106652701753307520}, abstractNote={The determination of a list of differentially expressed genes is a basic objective in many cDNA microarray experiments. We present a statistical approach that allows direct control over the percentage of false positives in such a list and, under certain reasonable assumptions, improves on existing methods with respect to the percentage of false negatives. The method accommodates a wide variety of experimental designs and can simultaneously assess significant differences between multiple types of biological samples. Two interconnected mixed linear models are central to the method and provide a flexible means to properly account for variability both across and within genes. The mixed model also provides a convenient framework for evaluating the statistical power of any particular experimental design and thus enables a researcher to a priori select an appropriate number of replicates. We also suggest some basic graphics for visualizing lists of significant genes. Analyses of published experiments studying human cancer and yeast cells illustrate the results.}, number={6}, journal={JOURNAL OF COMPUTATIONAL BIOLOGY}, author={Wolfinger, RD and Gibson, G and Wolfinger, ED and Bennett, L and Hamadeh, H and Bushel, P and Afshari, C and Paules, RS}, year={2001}, pages={625–637} }
 @article{gibson_2001, title={Developmental evolution: The unbearable likeness of beings}, volume={11}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(01)00190-7}, abstractNote={Comparative studies have revealed a remarkable range of genetic changes in the mechanisms that pattern the nematode vulva. Two new studies identify genetic variation within nematode species that affects cell division and competence in vulval precursors.}, number={9}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={2001}, month={May}, pages={R345–R348} }
 @article{gibson_palsson_2001, title={Evolution: A complement for evolutionary genetics}, volume={11}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(01)00014-8}, abstractNote={Developmental geneticists’ contribution to the study of the evolution of morphological divergence has proceeded along two lines: comparative analysis of gene expression and quantitative genetics. Recent studies highlight how complementation tests between species can bridge the gap between these approaches.}, number={2}, journal={CURRENT BIOLOGY}, author={Gibson, G and Palsson, A}, year={2001}, month={Jan}, pages={R74–R76} }
 @article{ashton_wagoner_carrillo_gibson_2001, title={Quantitative trait loci for the monoamine-related traits heart rate and headless behavior in Drosophila melanogaster}, volume={157}, number={1}, journal={Genetics}, author={Ashton, K. and Wagoner, A. P. and Carrillo, R. and Gibson, G.}, year={2001}, pages={283–294} }
 @article{jin_riley_wolfinger_white_passador-gurgel_gibson_2001, title={The contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster}, volume={29}, ISSN={["1061-4036"]}, DOI={10.1038/ng766}, abstractNote={Here we present a statistically rigorous approach to quantifying microarray expression data that allows the relative effects of multiple classes of treatment to be compared and incorporates analytical methods that are common to quantitative genetics. From the magnitude of gene effects and contributions of variance components, we find that gene expression in adult flies is affected most strongly by sex, less so by genotype and only weakly by age (for 1- and 6-wk flies); in addition, sex x genotype interactions may be present for as much as 10% of the Drosophila transcriptome. This interpretation is compromised to some extent by statistical issues relating to power and experimental design. Nevertheless, we show that changes in expression as small as 1.2-fold can be highly significant. Genotypic contributions to transcriptional variance may be of a similar magnitude to those relating to some quantitative phenotypes and should be considered when assessing the significance of experimental treatments.}, number={4}, journal={NATURE GENETICS}, author={Jin, W and Riley, RM and Wolfinger, RD and White, KP and Passador-Gurgel, G and Gibson, G}, year={2001}, month={Dec}, pages={389–395} }
 @article{gibson_wagner_2000, title={Canalization in evolutionary genetics: a stabilizing theory?}, volume={22}, DOI={10.1002/(SICI)1521-1878(200004)22:4<372::AID-BIES7>3.3.CO;2-A}, abstractNote={BioEssaysVolume 22, Issue 4 p. 372-380 Problems and Paradigms Canalization in evolutionary genetics: a stabilizing theory? Greg Gibson, Corresponding Author Greg Gibson ggibson@unity.ncsu.edu Department of Genetics, Gardner Hall, North Carolina State University, Raleigh, North Carolina.Gardner Hall, North Carolina State University, Raleigh, NC 27695-7614.Search for more papers by this authorGünter Wagner, Günter Wagner Department of Ecology and Evolutionary Biology, Osborn Memorial Labs, Yale University, New Haven, Connecticut.Search for more papers by this author Greg Gibson, Corresponding Author Greg Gibson ggibson@unity.ncsu.edu Department of Genetics, Gardner Hall, North Carolina State University, Raleigh, North Carolina.Gardner Hall, North Carolina State University, Raleigh, NC 27695-7614.Search for more papers by this authorGünter Wagner, Günter Wagner Department of Ecology and Evolutionary Biology, Osborn Memorial Labs, Yale University, New Haven, Connecticut.Search for more papers by this author First published: 17 March 2000 https://doi.org/10.1002/(SICI)1521-1878(200004)22:4<372::AID-BIES7>3.0.CO;2-JCitations: 261AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Canalization is an elusive concept. The notion that biological systems ought to evolve to a state of higher stability against mutational and environmental perturbations seems simple enough, but has been exceedingly difficult to prove. Part of the problem has been the lack of a definition of canalization that incorporates an evolutionary genetic perspective and provides a framework for both mathematical and empirical study. After briefly reviewing the importance of canalization in studies of evolution and development, we aim, with this essay, to outline a research program that builds upon the definition of canalization as the reduction in variability of a trait, and uses molecular genetic approaches to shed light on the problems of canalization. BioEssays 22:372–380, 2000. © 2000 John Wiley & Sons, Inc. Citing Literature Volume22, Issue4April 2000Pages 372-380 RelatedInformation}, number={4}, journal={BioEssays}, author={Gibson, G. and Wagner, G.}, year={2000}, pages={372–380} }
 @article{gibson_2000, title={Evolution: Hox genes and the cellared wine principle}, volume={10}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(00)00531-5}, abstractNote={Two Drosophila Hox genes involved in segmentation, fushi tarazu and bicoid, appear to have acquired these roles by functional divergence from classical homeotic genes. Recent results indicate how genes with critical functions in development can evolve completely different functions among species.}, number={12}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={2000}, month={Jun}, pages={R452–R455} }
 @article{birdsall_zimmerman_teeter_gibson_2000, title={Genetic variation for the positioning of wing veins in Drosophila melanogaster}, volume={2}, ISSN={["1525-142X"]}, DOI={10.1046/j.1525-142x.2000.00034.x}, abstractNote={SUMMARY To define the components of variation for wing shape in Drosophila in relation to what is known about the developmental control of wing patterning, we have characterized shape variation in the wings of 12 randomly chosen highly inbred lines. Despite large differences in wing size between males and females, and between flies reared at 18°C or 25°C, wing shape is remarkably unaffected by these variables and is highly line specific. The shape of each intervein region of the wing appears to be independently regulated at the genetic level, consistent with the role of secreted growth factors in establishing the locations of wing veins. Sex and temperature were found to have different effects on cell number in two intervein regions, with the result that wing shape is to a large extent independent of cell density. Dietary cholesterol was also shown to affect the breadth of the central intervein region, consistent with an effect on the strength of Hedgehog signaling during wing development. We conclude that wing shape is under tighter genetic control than wing size, and hypothesize that this control is achieved in large part by gene activity at the level of wing vein determination and differentiation.}, number={1}, journal={EVOLUTION & DEVELOPMENT}, author={Birdsall, K and Zimmerman, E and Teeter, K and Gibson, G}, year={2000}, pages={16–24} }
 @article{teeter_naeemuddin_gasperini_zimmerman_white_hoskins_gibson_2000, title={Haplotype dimorphism in a SNP collection from Drosophila melanogaster}, volume={288}, ISSN={["0022-104X"]}, DOI={10.1002/(SICI)1097-010X(20000415)288:1<63::AID-JEZ7>3.0.CO;2-1}, abstractNote={A moderate resolution single nucleotide polymorphism (SNP) map of the genome of Drosophila melanogaster that is designed for use in quantitative genetic mapping is described. Seventeen approximately 500 nucleotide gene sequences spaced at 10 to 20 centimorgan intervals were combined with 49 shorter sequence tag sites (STSs) at 5 to 10 centimorgan intervals to generate a map that should not leave any gaps greater than one half of a chromosome arm when any two wild type lines are compared. Of 20 markers with sufficient polymorphism to construct haplotype cladograms, 13 showed evidence for two divergent classes of haplotype. The possible mechanisms for and implications of the unexpected finding that two thirds of all short gene sequences in D. melanogaster may be dimorphic are discussed, including the suggestion that admixture between two separate lineages may have been a major event in the history of the species.}, number={1}, journal={JOURNAL OF EXPERIMENTAL ZOOLOGY}, author={Teeter, K and Naeemuddin, M and Gasperini, R and Zimmerman, E and White, KP and Hoskins, R and Gibson, G}, year={2000}, month={Apr}, pages={63–75} }
 @article{zimmerman_palsson_gibson_2000, title={Quantitative trait loci affecting components of wing shape in Drosophila melanogaster}, volume={155}, number={2}, journal={Genetics}, author={Zimmerman, E. and Palsson, A. and Gibson, G.}, year={2000}, pages={671–683} }
 @article{gasperini_gibson_1999, title={Absence of protein polymorphism in the Ras genes of Drosophila melanogaster}, volume={49}, ISSN={["0022-2844"]}, DOI={10.1007/PL00006579}, abstractNote={Sequence analysis of 27 alleles of each of the three Ras-related genes in Drosophila melanogaster indicates that they all have low levels of polymorphism but may experience slightly different evolutionary pressures. No amino acid replacement substitutions were indicated in any of the sequences, or in the sibling species D. simulans and D. mauritiana. The Dras1 gene, which is the major ras homologue in Drosophila, has less within-species variation in D. melanogaster relative to the amount of divergence from the sibling species than does Dras2, although the contrast was not significant by the HKA test. Dras2 appears to be maintaining two classes of haplotype in D. melanogaster, one of which is closer to the alleles observed in the sibling species, suggesting that this is not likely to be a pseudogene despite the absence of a mutant phenotype. Although differences in level of expression may affect the function of the genes, it is concluded that genetic variation in the Ras signal transduction pathways cannot be attributed to catalytic variation in the Ras proteins.}, number={5}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Gasperini, R and Gibson, G}, year={1999}, month={Nov}, pages={583–590} }
 @article{ahn_gibson_1999, title={Axial variation in the threespine stickleback: genetic and environmental factors}, volume={1}, ISSN={["1520-541X"]}, DOI={10.1046/j.1525-142x.1999.99009.x}, abstractNote={Subtle differences in the pattern of arrangement of types of vertebrae and associated median skeletal structures between a benthic and limnetic species pair of threespine stickleback from Paxton Lake, British Columbia, are typical of those found throughout the range of theGasterosteus aculeatusspecies complex. We established laboratory colonies from just three individuals of each species, and studied the effect of three generations of inbreeding on axial morphology. There was sufficient divergence in the location of individual elements between families to regenerate close to the entire range of axial diversity seen in threespine sticklebacks worldwide. Analysis of the patterns of variance and covariance between the axial locations of elements provides evidence for the action of both meristic and homeotic processes in the generation of morphological divergence within each species. Hybrid sticklebacks produced by the cross of limnetic and benthic parents tend to have intermediate morphologies, with dominance of either parental type evident for some elements. Effects of temperature and salinity were found to be small in direct comparison with between‐family effects, and varied according to genetic background. These results demonstrate that considerable genetic variation for axial morphology is maintained in natural populations of threespine stickleback, and that differences between populations may be brought about rapidly by changes in frequency of alleles that have coordinated effects along the body axis.}, number={2}, journal={EVOLUTION & DEVELOPMENT}, author={Ahn, DG and Gibson, G}, year={1999}, pages={100–112} }
 @article{gibson_1999, title={Developmental evolution: Going beyond the 'just so'}, volume={9}, ISSN={["1879-0445"]}, DOI={10.1016/S0960-9822(00)80111-6}, abstractNote={Two new protocols for infecting non-mammalian embryos with viruses, together with RNA inhibition, have provided evolutionary developmental biologists with the tools to study the effects of manipulating gene activity in a wide range of species, allowing them to test hypotheses rather than rely on inference from similarity.}, number={24}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={1999}, month={Dec}, pages={R942–R945} }
 @article{ahn_gibson_1999, title={Expression patterns of threespine stickleback Hox genes and insights into the evolution of the vertebrate body axis}, volume={209}, number={8}, journal={Development Genes and Evolution}, author={Ahn, D. G. and Gibson, G.}, year={1999}, pages={482–494} }
 @article{robbins_aggarwal_nichols_gibson_1999, title={Genetic variation affecting heart rate in Drosophila melanogaster}, volume={74}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672399003924}, abstractNote={Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2·5 to 
3·7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates 
that approaching one-quarter of the total variance in natural populations can be attributed to 
genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, 
which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate 
at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic 
backgrounds. This study provides a baseline for investigation of pharmacological and other 
physiological influences on heart rate in the model organism, and implies that quantitative genetic 
dissection will provide insight into the molecular basis for variation in normal and arrhythmic 
heart function.}, number={2}, journal={GENETICS RESEARCH}, author={Robbins, J and Aggarwal, R and Nichols, R and Gibson, G}, year={1999}, month={Oct}, pages={121–128} }
 @article{gibson_1999, title={Insect evolution: Redesigning the fruitfly}, volume={9}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(99)80056-6}, abstractNote={<h2>Abstract</h2> Homeotic mutations in <i>Drosophila</i> can result in dramatic phenotypes that suggest the possibility for rapid morphological evolution, but dissection of the genetic pathway downstream of <i>Ultrabithorax</i> is beginning to reveal how wing morphology may have evolved by more gradual transformations.}, number={3}, journal={CURRENT BIOLOGY}, author={Gibson, G}, year={1999}, month={Feb}, pages={R86–R89} }
 @article{gibson_wemple_van helden_1999, title={Potential variance affecting homeotic Ultrabithorax and Antennapedia phenotypes in Drosophila melanogaster}, volume={151}, number={3}, journal={Genetics}, author={Gibson, G. and Wemple, M. and Van Helden, S.}, year={1999}, pages={1081–1091} }