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Extensive epistasis for olfactory behaviour, sleep and waking activity in Drosophila melanogaster

  • SHILPA SWARUP (a1) (a2), SUSAN T. HARBISON (a1) (a2), LAUREN E. HAHN (a1), TATIANA V. MOROZOVA (a2) (a3), AKIHIKO YAMAMOTO (a2) (a3), TRUDY F. C. MACKAY (a1) (a2) and ROBERT R. H. ANHOLT (a1) (a2) (a3)
  • DOI:
  • Published online: 22 February 2012

Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insertions in Semaphorin-5C (Sema-5c) and Calreticulin (Crc), pleiotropic genes that affect olfactory behaviour and startle behaviour and, in the case of Crc, sleep phenotypes. We introduced Canton-S B (CSB) third chromosomes with or without a P-element insertion at the Crc or Sema-5c locus in multiple wild-derived inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and assessed the effects of epistasis on the olfactory response to benzaldehyde and, for Crc, also on sleep. In each case, we found substantial epistasis and significant variation in the magnitude of epistasis. The predominant direction of epistatic effects was to suppress the mutant phenotype. These observations support a previous study on startle behaviour using the same D. melanogaster chromosome substitution lines, which concluded that suppressing epistasis may buffer the effects of new mutations. However, epistatic effects are not correlated among the different phenotypes. Thus, suppressing epistasis appears to be a pervasive general feature of natural populations to protect against the effects of new mutations, but different epistatic interactions modulate different phenotypes affected by mutations at the same pleiotropic gene.

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*Corresponding author: Robert R. H. Anholt, Department of Biology, Box 7617, North Carolina State University, Raleigh, NC 27695-7617, USA. Tel: (919) 515-1173. Fax: (919) 515-1801. E-mail:
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R. R. H. Anholt & T. F. C. Mackay (2004). Quantitative genetic analyses of complex behaviours in Drosophila. Nature Reviews Genetics 5, 838849.

H. J. Bellen , R. W. Levis , G. Liao , Y. He , J. W. Carlson , G. Tsang , M. Evans-Holm , P. R. Hiesinger , K. L. Schulze , G. M. Rubin , R. A. Hoskins & A. C. Spradling (2004). The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167, 761781.

G. A. Brockmann , J. Kratzsch , C. S. Haley , U. Renne , M. Schwerin & S. Karle (2000). Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F(2). Variance of growth and obesity in DU6i×DBA/2 mice. Genome Research 10, 19411957.

O. Carlborg , L. Jacobsson , P. Ahgren , P. Siegel & L. Andersson (2006). Epistasis and the release of genetic variation during long-term selection. Nature Genetics 38, 418420.

J. M. Cheverud , T. T. Vaughn , L. S. Pletscher , A. C. Peripato , E. S. Adams , C. F. Erikson & K. J. King-Ellison (2001). Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice. Mammalian Genome 12, 3–12.

A. C. Edwards & T. F. C. Mackay (2009). Quantitative trait loci for aggressive behavior in Drosophila melanogaster. Genetics 182, 889897.

J. Flint & T. F. C. Mackay (2009). Genetic architecture of quantitative traits in mice, flies, and humans. Genome Research 19, 723733.

S. T. Harbison , M. A. Carbone , J. A. Ayroles , E. A. Stone , R. F. Lyman & T. F. C. Mackay (2009). Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep. Nature Genetics 41, 371375.

S. T. Harbison & A. Sehgal (2008). Quantitative genetic analysis of sleep in Drosophila melanogaster. Genetics 178, 23412360.

J. C. Hendricks , S. M. Finn , K. A. Panckeri , J. Chavkin , J. A. Williams , A. Sehgal & A. I. Pack (2000). Rest in Drosophila is a sleep-like state. Neuron 25, 129138.

W. G. Hill , M. E. Goddard & P. M. Visscher (2008). Data and theory point to mainly additive genetic variance for complex traits. PLoS Genetics 4, e1000008.

K. S. Ho & A. Sehgal (2005). Drosophila melanogaster: an insect model for fundamental studies of sleep. Methods in Enzymology 393, 772793.

K. W. Jordan , T. J. Morgan & T. F. C. Mackay (2006). Quantitative trait loci for locomotor behavior in Drosophila melanogaster. Genetics 174, 271284.

N. Khare , N. Fascetti , S. DaRocha , R. Chiquet-Ehrismann & S. Baumgartner (2000). Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis. Mechanisms of Development 91, 393397.

C. P. Klingenberg , L. J. Leamy & J. M. Cheverud (2004). Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics 166, 19091921.

J. Kroymann & T. Mitchell-Olds (2005). Epistasis and balanced polymorphism influencing complex trait variation. Nature 435, 9598.

J. Leips & T. F. C. Mackay (2002). The complex genetic architecture of Drosophila life span. Experimental Aging Research 28, 361390.

T. F. C. Mackay , S. Richards , E. A. Stone , A. Barbadilla , J. F. Ayroles , D. Zhu , S. Casillas , M. M. Magwire , J. M. Cridland , M. F. Richardson , R. R. H. Anholt , M. Barrón , C. Bess , K. P. Blankenburg , M. A. Carbone , D. Castellano , L. Chaboub , L. Duncan , Y. Han , Z. Harris , M. Javaid , J. C. Jayaseelan , S. N. Jhangiani , K. W. Jordan , F. Lara , F. Lawrence , S. L. Lee , P. Librado , R. S. Linheiro , R. F. Lyman , A. J. Mackey , M. Munidasa , D. M. Muzny , L. Nazareth , I. Newsham , L. Perales , L.-L. Pu , C. Qu , M. Ràmia , J. G. Reid , S. M. Rollmann , J. Rozas , L. Turlapati , K. C. Worley , Y.-Q. Wu , A. Yamamoto , Y. Zhu , C. M. Bergman , K. Thornton , D. Mittleman & R. A. Gibbs (2012). The Drosophila melanogaster Genetic Reference Panel. Nature 482, 173178.

T. F. C. Mackay , E. A. Stone & J. F. Ayroles (2009). The genetics of quantitative traits: challenges and prospects. Nature Reviews Genetics 10, 565577.

T. A. Manolio , F. S. Collins , N. J. Cox , D. B. Goldstein , L. A. Hindorff , D. J. Hunter , M. I. McCarthy , E. M. Ramos , L. R. Cardon , A. Chakravarti , J. H. Cho , A. E. Guttmacher , A. Kong , L. Kruglyak , E. Mardis , C. N. Rotimi , M. Slatkin , D. Valle , A. S. Whittemore , M. Boehnke , A. G. Clark , E. E. Eichler , G. Gibson , J. L. Haines , T. F. C. Mackay , S. A. McCarroll & P. M. Visscher (2009). Finding the missing heritability of complex diseases. Nature 461, 747753.

K. K. Norga , M. C. Gurganus , C. L. Dilda , A. Yamamoto , R. F. Lyman , P. H. Patel , G. M. Rubin , R. A. Hoskins , T. F. C. Mackay & H. J. Bellen (2003). Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development. Current Biology 13, 13881396.

P. C. Phillips (2008). Epistasis – the essential role of gene interactions in the structure and evolution of genetic systems. Nature Reviews Genetics 9, 855867.

P. J. Polaczyk , R. Gasperini & G. Gibson (1998). Naturally occurring genetic variation affects Drosophila photoreceptor determination. Development Genes and Evolution 207, 462470.

S. M. Rollmann , A. C. Edwards , A. Yamamoto , L. Zwarts , P. Callaerts , K. Norga , T. F. C. Mackay & R. R. H. Anholt (2008). Pleiotropic effects of Drosophila neuralized on complex behaviors and brain structure. Genetics 179, 13271336.

S. M. Rollmann , M. M. Magwire , T. J. Morgan , E. D. Özsoy , A. Yamamoto , T. F. C. Mackay & R. R. H. Anholt (2006). Pleiotropic fitness effects of the Tre1/Gr5a region in Drosophila. Nature Genetics 38, 824829.

S. M. Rollmann , A. Yamamoto , T. Goossens , L. Zwarts , Z. Callaerts-Vegh , P. Callaerts , K. Norga , T. F. C. Mackay & R. R. H. Anholt (2007). The early developmental gene Semaphorin 5c contributes to olfactory behavior in adult Drosophila. Genetics 176, 947956.

D. Sambandan , A. Yamamoto , J. J. Fanara , T. F. C. Mackay & R. R. H. Anholt (2006). Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster. Genetics 174, 13491363.

P. J. Shaw , C. Cirelli , R. J. Greenspan , & G. Tononi (2000). Correlates of sleep and waking in Drosophila melanogaster. Science 287, 18341837.

H. Sinha , L. David , R. C. Pascon , S. Clauder-Munster , S. Krishnakumar , M. Nguyen , G. Shi , J. Dean , R. W. Davis , P. J. Oefner , J. H. McCusker & L. M. Steinmetz (2008). Sequential elimination of major-effect contributors identifies additional quantitative trait loci conditioning high-temperature growth in yeast. Genetics 180, 16611670.

A. C. Spradling , H. J. Bellen & R. A. Hoskins (2011). Drosophila P elements preferentially transpose to replication origins. Proceedings of the Natural Academy of Sciences USA 108, 1594815953.

L. M. Steinmetz , H. Sinha , D. R. Richards , J. I. Spiegelman , P. J. Oefner , J. H. McCusker & R. W. Davis (2002). Dissecting the architecture of a quantitative trait locus in yeast. Nature 416, 326330.

J. R. Stoltzfus , W. J. Horton & M. S. Grotewiel (2003). Odor-guided behavior in Drosophila requires calreticulin. Journal of Comparative Physiology A. Neuroethology Sensory, Neural and Behavioral Physiology 189, 471483.

S. Swarup , T. I. Williams & R. R. H. Anholt (2011). Functional dissection of Odorant binding protein genes in Drosophila melanogaster. Genes Brain and Behavior 10, 648657.

B. van Swinderen & R. J. Greenspan (2005). Flexibility in a gene network affecting a simple behavior in Drosophila melanogaster. Genetics 169, 21512163.

A. Yamamoto , L. Zwarts , P. Callaerts , K. Norga , T. F. C. Mackay & R. R. H. Anholt (2008). Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster. Proceedings of the Natural Academy of Sciences USA 105, 1239312398.

L. Zwarts , M. M. Magwire , M. A. Carbone , M. Versteven , L. Herteleer , R. R. H. Anholt , P. Callaerts & T. F. C. Mackay (2011). Complex genetics architecture of Drosophila aggressive behavior. Proceedings of the Natural Academy of Sciences USA 108, 1707017075.

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