H Frederik Nijhout, Professor  

H Frederik Nijhout

Ph. D., Harvard University, 1974

Office Location: BioSci: 322
Office Phone: 919-684-4223
Email Address: hfn@duke.edu
Web Page: http://www.biology.duke.edu/nijhout/

Developmental Biology
Organismal Biology and Behavior

Research Categories: Developmental physiology/development and evolution

Research Description: Fred Nijhout is broadly interested in developmental physiology and in the interactions between development and evolution. He has several lines of research ongoing in his laboratory that on the surface may look independent from one another, but all share a conceptual interest in understanding how complex traits arise through, and are affected by, the interaction of genetic and environmental factors. 1) The control of polyphenic development in insects. This work attempts to understand how the insect developmental hormones, ecdysone and juvenile hormone, act to control alternative developmental pathways within a single individual. His studies and those of his students have dealt with the control of sequential polyphenism in metamorphosis, of alternate polyphenisms in caste determination of social insects and the many seasonal forms of insects. 2) The regulation of organ and body size in insects. Ongoing research deals with the mechanism by which insects asses their body size and stop growing when they have achieved a characteristic size. Other studies deal with the control of growth and size of imaginal disks. This work is revealing that the control of body and organ size does not reside in any specific cellular or molecular mechanism but that it is a systems property in which cellular, physiological and environmental signals all contribute in inextricable ways to produce the final phenotype. 3) The development and evolution of color patterns in Lepidoptera. Ongoing research attempts to elucidate the evolution of mimicry using genetic and genomic approaches. 4) The development, genetics and evolution of complex traits. Complex traits are those whose variation is affected by many genes and environmental factors and whose inheritance does not follow Mendel’s laws. In practice this involves understanding how genetic and developmental networks operate when there is allelic variation in their genes. This work attempts to reconstruct complex traits through mathematical models of the genetic and developmental processes by which they originate, and uses these models to study the effects of mutation and selection. Currently metabolic networks (e.g. folate metabolism) are being used to develop a deeper understanding of the functional relationships between genetic variation and trait variation, and of the mechanisms by which genetic and environmental variables interact to produce phenotypes. More on web page: http://www.biology.duke.edu/nijhout/

Representative Publications   (More Publications)   (search)

  1. Nijhout HF, German RZ., Developmental causes of allometry: new models and implications for phenotypic plasticity and evolution., Integr Comp Biol., vol. 52 no. 1 (July, 2012), pp. 43-52 [doi]  [abs].
  2. Ben-Shachar R, Chen Yi, Luo S, Hartman C, Reed MC, Nijhout HF, The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model, Theoretical Biology and Medical Modelling, vol. 9:55 (December, 2012) [doi] .
  3. Duncan TM, Reed MC, Nijhout HF., The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: A model., Mol. Nutr. Food Res., vol. 57 no. 4 (April, 2013), pp. 628-636 [doi]  [abs].
  4. Hines HM, Papa R, Ruiz M, Papanicolaou A, Wang C, Nijhout HF, McMillan WO, Reed RD., Transcriptome analysis reveals novel patterning and pigmentation genes underlying Heliconius butterfly wing pattern variation., BMC Genomics., vol. 13:288 (June, 2012), pp. 288 [doi]  [abs].
  5. Cho EH, Nijhout HF., Development of polyploidy of scale-building cells in the wings of Manduca sexta., Arthropod Struct Dev., vol. 42 no. 1 (January, 2013), pp. 37-46 [doi]  [abs].
  6. Davidowitz G, Nijhout HF, Roff DA., Predicting the response to simultaneous selection: genetic architecture and physiological constraints., Evolution, vol. 66 no. 9 (September, 2012), pp. 2916-2928 [doi]  [abs].
  7. Callier V, Nijhout HF., Supply-side constraints are insufficient to explain the ontogenetic scaling of metabolic rate in the tobacco Hornworm, Manduca sexta., PLoS One, vol. 7 no. 9 (September, 2012), pp. e45455 [doi]  [abs].
  8. Reed MC, Nijhout HF, Best JA., Mathematical insights into the effects of levodopa., Front Integr Neurosci, vol. 6:21 (July, 2012), pp. 21 [doi]  [abs].
  9. Padmanabha H, Correa F, Legros M, Nijhout HF, Lord C, Lounibos LP., An eco-physiological model of the impact of temperature on Aedes aegypti life history traits, J Insect Physiol., vol. 58 no. 12 (December, 2012), pp. 1597-1608 [doi]  [abs].
  10. Geenen S, du Preez FB, Reed M, Nijhout HF, Kenna JG, Wilson ID, Westerhoff HV, Snoep JL., A mathematical modelling approach to assessing the reliability of biomarkers of glutathione metabolism., Eur J Pharm Sci, vol. 46 no. 4 (July, 2012), pp. 233-243 [doi]  [abs].
  11. Obeid R, Hartmuth K, Herrmann W, Gortner L, Rohrer TR, Geisel J, Reed MC, Nijhout HF., Blood biomarkers of methylation in Down syndrome and metabolic simulations using a mathematical model., Mol Nutr Food Res., vol. 56 no. 10 (October, 2012), pp. 1582-1589 [doi]  [abs].
  12. Reed RD, Papa R, Martin A, Hines HM, Counterman BA, Pardo-Diaz C, Jiggins CD, Chamberlain NL, Kronforst MR, Chen R, Halder G, Nijhout HF, McMillan WO, optix Drives the Repeated Convergent Evolution of Butterfly Wing Pattern Mimicry, Science, vol. 333 (August 30, 2011), pp. 1137-1141 .
  13. Callier, VC and Nijhout HF, Control of body size by oxygen supply reveals size-dependent and size-independent mechanisms of molting and metamorphosis, PNAS, vol. 108 (2011), pp. 14664-14669 .
  14. Nijhout, HF, Dependence of morphometric allometries on the growth kinetics of body parts, Journal of Theoretical Biology, vol. 288 (August 15, 2011), pp. 35-43 .
  15. Lawley SD. Cinderella M, Hall MN, Nijhout, HF, Reed MC, Mathematical model insights into arsenic detoxification, Theoretical Biology and Medical Modelling, vol. 8 (August 1, 2011) [doi] .
  16. Moczek AP, Sultan S, Foster S, Ledon-Rettig C, Dworkin I, Nijhout HF, Abouheif E, Pfennig DW, The role of developmental plasticity in evolutionary innovation, Proceedings of the Royal Society B-Biological Sciences, vol. 278 (July, 2011), pp. 2705-2713 .
  17. Best J. Nijhout HF. Reed MC, Bursts and the efficacy of selective serotonin reuptake inhibitors, Pharmacopsychiatry, vol. 44 (May, 2011), pp. S76-S83 .
  18. Neuhouser ML, Nijhout HF, Gregory JF, Reed MC, James SJ, Liu A, Shane B, Ulrich CM, Mathematical modeling predicts the effect of folate deficiency and excess on cancer-related biomarkers, Cancer Epidemiology Biomarkers & Prevention, vol. 20 (July, 2011), pp. 1912-1917 .
  19. Nijhout HF, Grunert LW, The cellular and physiological mechanism of wing-body scaling in Manduca sexta., Science, vol. 330 (December, 2010), pp. 1693-1695 .
  20. Tobler A, Nijhout HF, Developmental constraints on the evolution of wing-body allometry in Manduca sexta, Evolution & Development, vol. 12 (November, 2010), pp. 57-66 .
  21. Nijhout HF, Molecular and physiological basis of colour pattern formation, Advances in Insect Physiology, vol. 38 (August, 2010), pp. 219-265 .
  22. Best J, Nijhout HF, Reed M, Serotonin synthesis, release and reuptake in terminals: a mathematical model, Theoretical Biology and Medical Modelling, vol. 7 (August, 2010), pp. 34ff .
  23. H.F. Nijhout, Photoperiodism in insects: effects on morphology, in Photoperiodism: The Biological Calendar, edited by Nelson RJ, Denlinger DL and Somers DE (August, 2010), pp. 318-341, Oxford University Press .
  24. Reed MC, Lieb A, Nijhout HF, The biological significance of substrate inhibition: A mechanism with diverse functions, BioEssays, vol. 32 (May, 2010), pp. 422-429 .
  25. Tobler A, Nijhout HF, A switch in the control of growth of the wing imaginal disks of Manduca sexta, PLoS-One, vol. 5 no. 5 (May, 2010), pp. e10723 .
  26. Best J, Reed M, Nijhout HF, Models of Dopaminergic and Serotonergic Signaling, Pharmacopsychiatry, vol. 43 (May, 2010), pp. S61-S66 .
  27. Diamond SE, Hawkins SD, Nijhout HF, Kingsolver, JG, Evolutionary divergence of field and laboratory populations of Manduca sexta in response to host-plant quality, Ecological Entomology, vol. 35 (April, 2010), pp. 166-174 .
  28. Nijhout HF, Roff DA, Davidowitz G, Conflicting processes in the evolution of body size and development time, Philosophical Transactions of the Royal Society B-Biological Sciences, vol. 365 (February, 2010), pp. 567-575 .
  29. Bowsher JH, Nijhout HF, Partial co-option of the appendage patterning pathway in the development of abdominal appendages in the sepsid fly Themira biloba, Development Genes and Evolution, vol. 219 (January, 2010), pp. 577-587 .
  30. Thomas DC, Conti DV, Baurley J, Nijhout HF, Reed MC, and Ulrich CM., Use of pathway information in molecular epidemiology., Human Genomics, vol. 4 (December, 2009), pp. 21-42 .
  31. Nijhout HF, Gregory JF, Fitzpatrick C1, Cho E, Lamers KY, Ulrich CM, Reed MC., A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism., Journal of Nutrition, vol. 139 (2009), pp. 784-791 .
  32. Howell AS, Savage NS, Johnson SA, Bose I, Wagner AW, Zyla TR, Nijhout HF, Reed MC, Goryachev AB and Lew DJ., Singularity in polarization: Rewiring yeast cells to make two buds., Cell, vol. 139 (2009), pp. 731-743 .
  33. Nijhout, HF, : Developmental phenotypic landscapes, Evolutionary Biology, vol. 35 (June, 2008), pp. 100-103 .
  34. Nijhout HF and Suzuki, Y., Environment and genetic accommodation., Biological Theory, vol. 3 no. 1-9 (2009) .
  35. Suzuki Y, Nijhout HF, Genetic basis of adaptive evolution of a polyphenism by genetic accommodation, Journal of Evolutionary Biology, vol. 21 (January, 2008), pp. 57-66 .
  36. Best JA, Nijhout HF, Reed MC., Homeostatic mechanisms in dopamine synthesis and release: a mathematical model., Theoretical Biology and Medical Modelling, vol. 6:21 (2009) .
  37. Nijhout HF, Reed MC, A mathematical model for the regulation of juvenile hormone titers, J. Insect Physiology, vol. 54 (January, 2008), pp. 255-264 .
  38. Reed M, Best J, Nijhout HF., Passive and active stabilization of dopamine in the striatum., Bioscience Hypotheses, vol. 2 (2009), pp. 240-244. .
  39. Leduc, D., Escartin, F., Nijhout, H.F., Reed, M.C., Liebl, U., Skouloubris, S. and Myllykallio, H., Flavin-dependent thymidylate synthase ThyX activity: Implications for the folate cycle in bacteria., J. Bacteriol., vol. 189 (2007), pp. 8537-8545 .
  40. Suzuki Y, Nijhout HF, Constraint and developmental dissociation of phenotypic integration in a genetically accommodated trait, Evolution & Development, vol. 10 (November, 2008), pp. 690-699 .
  41. Reed R.D., Chen P.H. and Nijhout, H.F., Cryptic variation in butterfly eyespot development: the importance of sample size in gene expression studies, Evolution & Development, vol. 9 (2007), pp. 2-9 .
  42. Nijhout, HF, Size matters (but so does time), and It's OK to be different, Developmental Cell, vol. 15 (October, 2008), pp. 491-492 .
  43. Nijhout, H.F, Smith, W.A. Schachar, I, Subramanian, S., Tobler, A. and Grunert, L.W., The control of growth and differentiation of the wing imaginal disks of Manduca sexta., Dev. Biol., vol. 302 (2007), pp. 569-576 .
  44. Nijhout HF, Reed M, Ulrich C., Mathematical models of one-carbon metabolism, Vitamins and Hormones, vol. 79 (September, 2008), pp. 45-82 .
  45. Shingleton, A.W., Frankino, W.A., Flatt, T., Nijhout, H.F. and Emlen, D.J., Size and shape: the developmental regulation of static allometry in insects., BioEssays, vol. 29 (2007), pp. 536-548 .
  46. Ulrich CM, Reed MC, Nijhout HF, : Modeling folate, one-carbon metabolism, and DNA methylation, Nutrition Reviews, vol. 8 (August, 2008), pp. : S27-S30 .
  47. Brandon, R.N. and Nijhout, H.F., The empirical non-equivalence of genic and genotypic models of selection: A decisive refutation of genic selectionism and pluralistic genic selectionism., Philosophy of Science, vol. 73 (2007), pp. 277-297 .
  48. Ulrich CM, Neuhouser M, Liu A, Boynton A, Gregory JF, Shane B, James SJ, Reed MC, Nijhout HF., Mathematical modeling of folate metabolism: Predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis, Cancer Epidemiology Biomarkers & Prevention, vol. 17 (July, 2008), pp. 1822-1831 .
  49. Bowsher, J.H. and Nijhout, H.F., Evolution of novel abdominal appendages in a sepsid fly from histoblasts, not imaginal discs., Evolution & Development, vol. 9 (2007), pp. 347-354 .
  50. Reed MC, Thomas R, Pavisic J, Nijhout HF, James SJ, Ulrich CM., A mathematical model of glutathione metabolism, Theoretical Biology and Medical Modelling, vol. 5 no. 8 (July, 2008), pp. doi:10.1186/1742-4682-5-8  [abs].
  51. Anderson, D., Mattingly, J., Nijhout, H. F., and Reed, M.C., Propagation of fluctuations in biochemical systems, I. Linear SSC networks., . Bull. Math. Biol., vol. 69 (2007), pp. 1791-1813 .
  52. Suzuki, Y. and Nijhout, H.F, Genetic basis of adaptive evolution of a polyphenism by genetic accommodation., J. Evol. Biol. (in press) (2007) .
  53. Nijhout, H.F. and Reed, M.J., A mathematical model for the regulation of juvenile hormone titers., J. Insect Physiol. (in press) (2007) .
  54. Nijhout, H.F., Reed, M.C. and Ulrich, C.M., A day in the life of cell metabolism., Biological Theory (in press) (2007) .
  55. H.F. Nijhout, Stochastic gene expression: dominance, thresholds and boundaries., in Dominance and Haploinsufficiency, edited by Veitia, R.A. (2006), pp. 61-75, Landes Press .
  56. Suzuki, Y. and Nijhout, H.F., Evolution of a polyphenism by genetic accommodation., Science, vol. 311 (2006), pp. 650-652 .
  57. Nijhout HF, Reed MC, Lam S-L,Shane B, Gregory JF, and Ulrich CM., In silico experimentation with a model of hepatic mitochondrial folate metabolism., Theoretical Biology and Medical Modelling, vol. 3 (2006), pp. 40ff .
  58. Nijhout, H. F., Reed, M., Anderson, D., Mattingly, J., James, S. J., and Ulrich, C. M., Long-range allosteric interactions between the folate and methionine cycles stabilize DNA methylation rate., Epigenetics, vol. 1 no. 2 (2006), pp. 81-87 .
  59. Davidowitz, G. Roff, D.A. and Nijhout, H.F., A physiological perspective on the response of body size and development time to simultaneous directional selection., Integr. Comp. Biol., vol. 45 (2005), pp. 525-531 .
  60. Boyles, A.L. Billups, A.V., Deak, K.L., Siegel, D.G., Mehltretter, L., Slifer, S.H. Bassuk, A.G., Kessler, J.A., Reed, M.C. Nijhout, H.F. George, T.M., Enterline, D.S., Gilbert, J.R., Speer, M.C., and the NTD Collaborative Group., Neural tube defects and folate pathway genes: family-based association tests of gene–gene and gene–environment interactions., Environ. Health Perspect., vol. 114 (2006), pp. 1547-1552 .
  61. B.A.Edgar and H.F. Nijhout, Growth and cell cycle control in Drosophila, in Cell Growth: Control of Cell Size, Cold Spring Harbor Monographs, edited by M.N. Hall, M.Raff and G. Thomas (2004), pp. 23-83, Cold Spring Harbor Laboratory Press .
  62. Reed, M.C., Nijhout, H.F., Neuhouser, M.L., Gregory J.F. III., Shane, B., James, S.J., Boynton, A. and Ulrich, C.M., A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism., J. Nutr., vol. 136 (2006), pp. 2653-2661 .
  63. Yang AS, Martin CH, Nijhout HF, Geographic variation of caste structure among ant populations, CURRENT BIOLOGY, vol. 14 (2004), pp. 514-519 .
  64. Ulrich , C.M., Nijhout , H.F. and Reed, M.C., Mathematical modeling: epidemiology meets systems biology., Cancer Epidemiol. Biomarkers Prev., vol. 15 (2006), pp. 827-829 .
  65. Moczek AP, Nijhout HF, Trade-offs during the development of primary and secondary sexual traits in a horned beetle, AMERICAN NATURALIST, vol. 163 (2004), pp. 184-191 .
  66. Veitia, R. and Nijhout, H.F., The robustness of the transcriptional response to alterations in morphogenetic gradients., BioEssays, vol. 28 (2006), pp. 282-289 .
  67. Davidowitz G, D'Amico LJ, Nijhout HF, The effects of environmental variation on a mechanism that controls insect body size, EVOLUTIONARY ECOLOGY RESEARCH, vol. 6 (2004), pp. 49-62 .
  68. Nijhout, H.F., Davidowitz, G. and Roff, D.A., A quantitative analysis of the mechanism that controls body size in Manduca sexta., Journal of Biology, vol. 5 no. 16 (2006), pp. 1-16 .
  69. H.F. Nijhout, M.C.Reed, P.Budu and C., A mathematical model of the folate cycle: New insights into folate homeostasis, Journal of Biological Chemistry, vol. 279 (2004), pp. 55008-55016 .
  70. Reed, M.C., Nijhout, H.F., Sparks, R. and Ulrich, N., A mathematical model of the methionine cycle, J. Theoret. Biol., vol. 226 (2004), pp. 33-43 .
  71. Nijhout, H.F. and G. Davidowitz., Developmental perspectives on phenotypic plasticity, canalization, and fluctuating asymmetry., in Developmental Instability: Causes and Consequences, edited by M. Polak (2003), pp. 3-13, MIT Press .
  72. H.F. Nijhout, Polymorphic mimicry in Papilio dardanus: mosaic dominance, big effects and origins., Evolution & Development, vol. 5 (2003), pp. 579-592 .
  73. Nijhout, H.F., Maini, P.K., Madzvamuse, A., Wathen, A. and Sekimura, T., Pigmentation pattern formation in butterflies --Experiments and models., Comptes Rendus Biologies, vol. 328 (2003), pp. 717-727 .
  74. Wheeler, D.E. and Nijhout, H.F., A perspective for understanding the modes of juvenile hormone action as a lipid signaling system., BioEssays, vol. 25 (2003), pp. 994-1001 .
  75. H.F. Nijhout, On the association between genes and complex traits., J. Invest. Dermatol., vol. 8 (2003), pp. 162-163 .
  76. H.F. Nijhout, The control of body size in insects., Developmental Biology, vol. 261 (2003), pp. 1-9 .
  77. H.F. Nijhout, The importance of context in genetics, American Scientist, vol. 91 (2003), pp. 416-423 .
  78. Nijhout, H.F., Berg, A.M. and Gibson, W.T., A mechanistic study of evolvability using the mitogen activated protein kinase cascade., Evolution & Development, vol. 5 (2003), pp. 281-294 .
  79. Moczek, A.P. and Nijhout, H.F., Rapid evolution of a polyphenic threshold., Evolution & Development, vol. 5 (2003), pp. 259-268 .
  80. H.F. Nijhout, The development and evolution of adaptive polyphenisms., Evolution & Development, vol. 5 (2003), pp. 9-18 .
  81. Davidowitz, G., D’Amico. L.J. and H.F. Nijhout., Critical weight in the development of insect body size., Evolution & Development, vol. 5 (2003), pp. 188-197 .
  82. H.F. Nijhout, The control of growth, Development, vol. 130 (2003), pp. 5863-5867 .
  83. H.F. Nijhout, Gradients, diffusion and genes in pattern formation, in Origination of Organismal Form, edited by G. Müller and S. Newman, (2003), MIT Press .
  84. Koch, P.B. and H.F. Nijhout, The role of wing veins in colour pattern development in the butterfly Papilio xuthus (Lepidoptera: Papilionidae)., European Journal of Entomology, vol. 99 (2002), pp. 67-72 .
  85. H.F. Nijhout, The nature of robustness in development., BioEssays, vol. 24 (2002), pp. 553-563 .
  86. H.F. Nijhout, Genetic regulatory networks., in Encyclopedia of Evolution. (2002), Oxford University Press. .
  87. Nijhout, H.F. and Grunert, L.W., Bombyxin is a growth factor for wing imaginal disks in Lepidoptera, Proc. Nat. Acad. Sci., vol. 99 (2002), pp. 15446-15450 .
  88. Nijhout, H.F. and G. Davidowitz., Developmental perspectives on phenotypic plasticity, canalization, and fluctuating asymmetry., in Developmental Instability: Causes and Consequences, edited by M. Polak (2002), Oxford University Press .
  89. Moczek, AP and HF Nijhout, Developmental mechanism of threshold evolution in a polyphenic beetle, Evolution & Development, vol. 4 (2002), pp. 252-264 .
  90. H.F. Nijhout, The ontogeny of phenotypes, in Cycles of Contingency, pp.129-140, edited by S oyama, P Griffiths and R Gray (2001), MIT Press .
  91. Moczek, AP and HF Nijhout, A method for sexing third instar larvae of the genus Onthophagus Latreille (Coleoptera Scarabeidae), Coleopt. Bull. (2001) .
  92. H.F. Nijhout, Origin of butterfly wing patterns, in The Character Concept in Evolutionary Biology, pp.511-529, edited by GA Wagner (2001), Academic Press .
  93. Gilchrist, MA and HF Nijhout, Non-linear developmental processes as sources of dominance, Genetics, vol. 159 (2001), pp. 423-432 .
  94. Shafiei, M, AP Moczek, and HF Nijhout, Food availability controls the onset of metamorphosis in the dung beetle Onthophagus taurus (Cleoptera: Scarabeidae), Physiol. Entomol, vol. 26 (2001), pp. 173-180 .
  95. Emlen, DJ and HF Nijhout, Hormonal control of horn length dimorphism in Onthophagus taurus (Coleoptera: Scarabeidae): a second critical period of sensitivity to juvenile hormone, J. Insect Physiol., vol. 47 (2001), pp. 1045-1054 .
  96. Browder, MH, LJ D'Amico and HF Nijhout, The Role of Low Levels of Juvenile Hormone Esterase in the Metamorphosis of Manduca sexta., J. Insect Science, vol. 1 no. 11 (2001), pp. 1-5 .
  97. McDonald, AK and HF Nijhout, The effect of environmental conditions on mating activity of the Buckeye butterfly, Precis coenia, J. Res. Lepidopt., vol. 35 no. 22-28 (2000) .
  98. Emlen, DJ and HF Nijhout, The development and evolution of exaggerated morphologies in insects., Ann. Rev. Entomol., vol. 45 (2000), pp. 661-708 .
  99. Miner, AL, AJ Rosenberg and HF Nijhout, Control of growth and differentiation of the wing imaginal disks of Precis coenia (Lepidoptera: Nymphalidae), J. Insect Physiol., vol. 46 (2000), pp. 251-258 .
  100. D' Amico, LJ, G Davidowitz and HF Nijhout, The developmental and physiological basis of body size evolution in an insect, Proc. Roy. Soc. London, vol. B 268 (2001), pp. 1589-1593 .