@article{wilson_morgan_mackay_2006, title={High-resolution mapping of quantitative trait loci affecting increased life span in Drosophila melanogaster}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.055111}, abstractNote={Abstract Limited life span and senescence are near-universal characteristics of eukaryotic organisms, controlled by many interacting quantitative trait loci (QTL) with individually small effects, whose expression is sensitive to the environment. Analyses of mutations in model organisms have shown that genes affecting stress resistance and metabolism affect life span across diverse taxa. However, there is considerable segregating variation for life span in nature, and relatively little is known about the genetic basis of this variation. Replicated lines of Drosophila that have evolved increased longevity as a correlated response to selection for postponed senescence are valuable resources for identifying QTL affecting naturally occurring variation in life span. Here, we used deficiency complementation mapping to identify at least 11 QTL on chromosome 3 that affect variation in life span between five old (O) lines selected for postponed senescence and their five base (B) population control lines. Most QTL were sex specific, and all but one affected multiple O lines. The latter observation is consistent with alleles at intermediate frequency in the base population contributing to the response to selection for postponed senescence. The QTL were mapped with high resolution and contained from 12 to 170 positional candidate genes.}, number={3}, journal={GENETICS}, author={Wilson, Rhonda H. and Morgan, Theodore J. and Mackay, Trudy F. C.}, year={2006}, month={Jul}, pages={1455–1463} } @article{carbone_jordan_lyman_harbison_leips_morgan_deluca_awadalla_mackay_2006, title={Phenotypic variation and natural selection at Catsup, a pleiotropic quantitative trait gene in Drosphila}, volume={16}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2006.03.051}, abstractNote={Quantitative traits are shaped by networks of pleiotropic genes [1Mackay T.F.C. The genetic architecture of quantitative traits.Annu. Rev. Genet. 2001; 35: 303-339Crossref PubMed Scopus (753) Google Scholar]. To understand the mechanisms that maintain genetic variation for quantitative traits in natural populations and to predict responses to artificial and natural selection, we must evaluate pleiotropic effects of underlying quantitative trait genes and define functional allelic variation at the level of quantitative trait nucleotides (QTNs). Catecholamines up (Catsup), which encodes a negative regulator of tyrosine hydroxylase [2Stathakis D.G. Burton D.Y. McIvor W.E. Krishnakumar S. Wright T.R. O'Donnell J.M. The Catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.Genetics. 1999; 153: 361-382Crossref PubMed Google Scholar], the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster [2Stathakis D.G. Burton D.Y. McIvor W.E. Krishnakumar S. Wright T.R. O'Donnell J.M. The Catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.Genetics. 1999; 153: 361-382Crossref PubMed Google Scholar, 3O'Donnell J.M. Wang Z. Chaudhuri A. Effects of perturbation of catecholamine regulation on resistance of Drosophila melanogaster to environmental stress.in: Blau N. Thony B. Pterins, Folates, and Related Biogenic Amines. SPS Publications, Heilbronn2004: 94-100Google Scholar, 4Mackay T.F.C. Roshina N.V. Leips J.W. Pasyukova E.G. Complex genetic architecture of Drosophila longevity.in: Masaro E.J. Austad S.N. Handbook of the Biology of Aging. Sixth Edition. Elsevier Press, Burlington2005: 181-216Crossref Scopus (24) Google Scholar]. We used association mapping to determine whether the same or different QTNs at Catsup are associated with naturally occurring variation in multiple quantitative traits. We sequenced 169 Catsup alleles from a single population and detected 33 polymorphisms with little linkage disequilibrium (LD). Different molecular polymorphisms in Catsup are independently associated with variation in longevity, locomotor behavior, and sensory bristle number. Most of these polymorphisms are potentially functional variants in protein coding regions, have large effects, and are not common. Thus, Catsup is a pleiotropic quantitative trait gene, but individual QTNs do not have pleiotropic effects. Molecular population genetic analyses of Catsup sequences are consistent with balancing selection maintaining multiple functional polymorphisms.}, number={9}, journal={CURRENT BIOLOGY}, author={Carbone, Mary Anna and Jordan, Katherine W. and Lyman, Richard F. and Harbison, Susan T. and Leips, Jeff and Morgan, Theodore J. and DeLuca, Maria and Awadalla, Philip and Mackay, Trudy F. C.}, year={2006}, month={May}, pages={912–919} } @article{rollmann_magwire_morgan_ozsoy_yamamoto_mackay_anholt_2006, title={Pleiotropic fitness effects of the Tre1-Gr5a region in Drosophila melanogaster}, volume={38}, ISSN={["1546-1718"]}, DOI={10.1038/ng1823}, abstractNote={The abundance of transposable elements and DNA repeat sequences in mammalian genomes raises the question of whether such insertions represent passive evolutionary baggage or may influence the expression of complex traits. We addressed this question in Drosophila melanogaster, in which the effects of single transposable elements on complex traits can be assessed in genetically identical individuals reared in controlled environments. Here we demonstrate that single P-element insertions in the intergenic region between the gustatory receptor 5a (Gr5a, also known as Tre) and trapped in endoderm 1 (Tre1), which encodes an orphan receptor, exert complex pleiotropic effects on fitness traits, including selective nutrient intake, life span, and resistance to starvation and heat stress. Mutations in this region interact epistatically with downstream components of the insulin signaling pathway. Transposon-induced sex-specific and sex-antagonistic effects further accentuate the complex influences that intergenic transposable elements can contribute to quantitative trait phenotypes.}, number={7}, journal={NATURE GENETICS}, author={Rollmann, Stephanie M. and Magwire, Michael M. and Morgan, Theodore J. and Ozsoy, Ergi D. and Yamamoto, Akihiko and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2006}, month={Jul}, pages={824–829} } @article{edwards_rollmann_morgan_mackay_2006, title={Quantitative genomics of aggressive behavior in Drosophila melanogaster}, volume={2}, ISSN={["1553-7390"]}, DOI={10.1371/journal.pgen.0020154}, abstractNote={Aggressive behavior is important for animal survival and reproduction, and excessive aggression is an enormous social and economic burden for human society. Although the role of biogenic amines in modulating aggressive behavior is well characterized, other genetic mechanisms affecting this complex behavior remain elusive. Here, we developed an assay to rapidly quantify aggressive behavior in Drosophila melanogaster, and generated replicate selection lines with divergent levels of aggression. The realized heritability of aggressive behavior was approximately 0.10, and the phenotypic response to selection specifically affected aggression. We used whole-genome expression analysis to identify 1,539 probe sets with different expression levels between the selection lines when pooled across replicates, at a false discovery rate of 0.001. We quantified the aggressive behavior of 19 mutations in candidate genes that were generated in a common co-isogenic background, and identified 15 novel genes affecting aggressive behavior. Expression profiling of genetically divergent lines is an effective strategy for identifying genes affecting complex traits.}, number={9}, journal={PLOS GENETICS}, author={Edwards, Alexis C. and Rollmann, Stephanie M. and Morgan, Theodore J. and Mackay, Trudy F. C.}, year={2006}, month={Sep}, pages={1386–1395} } @article{morgan_mackay_2006, title={Quantitative trait loci for thermotolerance phenotypes in Drosophila melanogaster}, volume={96}, ISSN={["1365-2540"]}, DOI={10.1038/sj.hdy.6800786}, abstractNote={For insects, temperature is a major environmental variable that can influence an individual's behavioral activities and fitness. Drosophila melanogaster is a cosmopolitan species that has had great success in adapting to and colonizing diverse thermal niches. This adaptation and colonization has resulted in complex patterns of genetic variation in thermotolerance phenotypes in nature. Although extensive work has been conducted documenting patterns of genetic variation, substantially less is known about the genomic regions or genes that underlie this ecologically and evolutionarily important genetic variation. To begin to understand and identify the genes controlling thermotolerance phenotypes, we have used a mapping population of recombinant inbred (RI) lines to map quantitative trait loci (QTL) that affect variation in both heat- and cold-stress resistance. The mapping population was derived from a cross between two lines of D. melanogaster (Oregon-R and 2b) that were not selected for thermotolerance phenotypes, but exhibit significant genetic divergence for both phenotypes. Using a design in which each RI line was backcrossed to both parental lines, we mapped seven QTL affecting thermotolerance on the second and third chromosomes. Three of the QTL influence cold-stress resistance and four affect heat-stress resistance. Most of the QTL were trait or sex specific, suggesting that overlapping but generally unique genetic architectures underlie resistance to low- and high-temperature extremes. Each QTL explained between 5 and 14% of the genetic variance among lines, and degrees of dominance ranged from completely additive to partial dominance. Potential thermotolerance candidate loci contained within our QTL regions are identified and discussed.}, number={3}, journal={HEREDITY}, author={Morgan, TJ and Mackay, TFC}, year={2006}, month={Mar}, pages={232–242} } @article{mackay_heinsohn_lyman_moehring_morgan_rollmann_2005, title={Genetics and genomics of Drosophila mating behavior}, volume={102}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0501986102}, abstractNote={ The first steps of animal speciation are thought to be the development of sexual isolating mechanisms. In contrast to recent progress in understanding the genetic basis of postzygotic isolating mechanisms, little is known about the genetic architecture of sexual isolation. Here, we have subjected Drosophila melanogaster to 29 generations of replicated divergent artificial selection for mating speed. The phenotypic response to selection was highly asymmetrical in the direction of reduced mating speed, with estimates of realized heritability averaging 7%. The selection response was largely attributable to a reduction in female receptivity. We assessed the whole genome transcriptional response to selection for mating speed using Affymetrix GeneChips and a rigorous statistical analysis. Remarkably, >3,700 probe sets (21% of the array elements) exhibited a divergence in message levels between the Fast and Slow replicate lines. Genes with altered transcriptional abundance in response to selection fell into many different biological process and molecular function Gene Ontology categories, indicating substantial pleiotropy for this complex behavior. Future functional studies are necessary to test the extent to which transcript profiling of divergent selection lines accurately predicts genes that directly affect the selected trait. }, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Mackay, TFC and Heinsohn, SL and Lyman, RF and Moehring, AJ and Morgan, TJ and Rollmann, SM}, year={2005}, month={May}, pages={6622–6629} } @article{morgan_evans_garland_swallow_carter_2005, title={Molecular and quantitative genetic divergence among populations of house mice with known evolutionary histories}, volume={94}, number={5}, journal={Heredity}, author={Morgan, T. J. and Evans, M. A. and Garland, T. and Swallow, J. G. and Carter, P. A.}, year={2005}, pages={518–525} } @article{morgan_garland_carter_2003, title={Ontogenies in mice selected for high voluntary wheel-running activity. I. Mean ontogenies}, volume={57}, ISSN={["0014-3820"]}, DOI={10.1111/j.0014-3820.2003.tb01556.x}, abstractNote={Abstract The evolutionary importance of postnatal ontogenies has long been recognized, but most studies of ontogenetic trajectories have focused exclusively on morphological traits. For animals, this represents a major omission because behavioral traits and their ontogenies often have relatively direct relationships to fitness. Here four replicate lines of house mice artificially selected for high early‐age wheel running and their four replicate control lines were used to evaluate the effects of early‐age directional selection, genetic drift, and activity environment (presence or absence of a running wheel) on variation in the ontogenies of three traits known to be genetically correlated: voluntary wheel running, body mass, and food consumption. Early‐age selection significantly changed both the shape and position of the wheel‐running and food‐consumption ontogenies while influencing the position, but not the shape, of the body mass ontogeny. Genetic drift (as indicated by variation among replicate lines) produced significant changes in both the position and shape of all three ontogenies; however, its effect differed between the selection and control groups. For wheel running and food consumption, genetic drift only influenced the control ontogenies, whereas for body mass, genetic drift had a significant effect in both selection groups. Both body‐mass and food‐consumption ontogenies were significantly altered by activity environment, with the environment causing significant changes in the shape and position of both ontogenies. Overall the results demonstrate strong effects of early‐age selection, genetic drift, and environmental variation on the evolution and expression of behavioral and morphological ontogenies, with selection changing only the position of the morphological ontogeny but both the position and shape of the behavioral ontogenies.}, number={3}, journal={EVOLUTION}, author={Morgan, TJ and Garland, T and Carter, PA}, year={2003}, month={Mar}, pages={646–657} } @article{morgan_garland_irwin_swallow_carter_2003, title={The mode of evolution of molecular markers in populations of house mice under artificial selection for locomotor behavior}, volume={94}, ISSN={["1465-7333"]}, DOI={10.1093/jhered/esg021}, abstractNote={A complete understanding of the mode of evolution of molecular markers is important for making inferences about different population genetic parameters, especially because a number of studies have reported patterns of allelic variation at molecular markers that are not in agreement with neutral evolutionary expectations. In the present study, house mice (Mus domesticus) from the fourteenth generation of a selection experiment for increased voluntary wheel-running activity were used to test how selection on a complex behavior affects the distribution of allelic variation by examining patterns of variation at six microsatellite and four allozyme loci. This population had a hierarchical structure that allowed for simultaneous testing of the effects of selection and genetic drift on the distribution of allelic variation by comparing observed patterns of allele frequencies and estimates of genetic divergence at multiple hierarchical levels to expectations under models of neutral evolution. The levels of genetic divergence among replicate lines and between selection groups, estimated from microsatellite data or pooled microsatellite and allozyme data, were not significantly different from expectations under neutral evolution. Furthermore, the pattern of change of allele frequencies between the base population and generation 14 was largely in agreement with expectations under neutral evolution (although the PGM locus exhibited a pattern of change within populations that was difficult to explain under neutral evolution). Overall the results generally provide support for the neutral evolution of molecular markers.}, number={3}, journal={JOURNAL OF HEREDITY}, author={Morgan, TJ and Garland, T and Irwin, BL and Swallow, JG and Carter, PA}, year={2003}, month={May}, pages={236–242} } @article{jordan_carbone_yamamoto_morgan_mackay, title={Quantitative genomics of locomotor behavior in Drosophila melanogaster}, volume={8}, number={8}, journal={Genome Biology}, author={Jordan, K. W. and Carbone, M. A. and Yamamoto, A. and Morgan, T. J. and Mackay, T. F.} }