Post on 21-Dec-2015
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Single gene effects on behavior
• How do gene products affect behavior?
• What methods are used to study single-gene effects?– Segregation analysis– Gene mapping– Differences in mRNA between individuals
or cell types correlates with behavior– Genetic engineering
How do gene products affect behavior?
• If the central dogma is correct, i.e.:
• DNA sequence -> mRNA sequence -> amino acid sequence = protein
• How can a change in the DNA sequence influence behavior of the adult organism?
Examples of how proteins can influence behavior
• Peptide hormones act as neurotransmitters– Dopamine, serotonin, oxytocin, vasopressin
• Steroid hormone receptors allow responses to hormones• Signaling peptides can activate ion channels and alter
neuronal sensitivity• Pigments can alter perception• Neuronal growth factors alter development• Transcription factors bind to DNA and can alter the
amount and timing of transcription of other genes
Methods for studying single gene effects on behavior
• Find alternate alleles at a single locus– Segregation analysis
• Natural variants• Create mutations (x-rays, EMS-ethylene methyl sulfide)
– Gene mapping and association
• Find differences in expression of candidate genes– Genetic mosaics– Expression studies
• Northerns, microarrays, quantitative RT-PCR
– Transgenics• substitutions, knockouts, viral-mediated gene transfer
Simple segregation patterns
• Two phenotypes– 3:1 ratio of offspring
• AA x aa = (AA + 2Aa) + aa (A dominant, ex. tongue rolling)
– 1:1 ratio of offspring• Aa x aa = Aa + aa (A dominant or codominant)
• Aa x AY = AY + aY males (A dominant and on X, ex. red-green color blindness in males)
• Three phenotypes– 1:2:1 ratio of offspring
• AA x aa = AA + 2Aa + aa (A codominant)
Dominance
• Exists whenever the phenotype of a heterozygote is not the average of the parental values
• Attribute of a genotype, not an allele• May be scale dependent• Only relationships which can share
genotypes can share dominance, e.g. full-sibs, twins
aa Aa AA
Phe
noty
pe
aa Aa AA
Phe
noty
pe
No dominance = additive
Complete dominance
aa Aa AA
Phe
noty
pe
Overdominance
The foraging gene
• Rover allele is favored in crowded environments while sitter allele is favored at low densities
• Expression of rover can be altered by restricting food
• Located on chr 2, codes for an enzyme (cyclic GMP-dependent kinase) involved in cell signaling that influences how larvae respond to food quality
Gene mapping
• Genotype individuals from known pedigrees or from a segregating cross involving inbred strains (F2 or backcross)
• Measure trait of interest
• Find association between trait and marker presence
RFLP association with Huntington’s chorea
Note that 33 of 34 affected individuals have the C allele; indicating1 recombination event and tight linkage between C and HD genes
Drosophila gynandromorphs (genetic mosaics)Has been used to study where X-linked genes are expressed
during the first cell division
Transformation experiments show that per affects Drosophila male courtship
D. melanogaster and D. simulans differ in the interpulse interval (IPI) in male courtship song.
The species differences are retained when pero mutant flies are transformed with conspecificperiod genes.
Cross species transformations with per altered male behavior to approximate the other species.
Epistasis - genetic backgroundaffects behavior
Fly memory and dunce,rutabaga
• dunce flies can’t form association between chemical odor and shock
• Not a sensory problem• Have poor memory - association
doesn’t last as long as normal• rutabaga also causes poor learning and
memory
Memory formation in flies
rutabaga has defectiveadenyl-cyclase, whichforms cAMP from ATP
dunce codes an enzymecAMP phosphodiesterase, which breaks down cAMP
Cyclic AMP Response Binding proteinThis pathway is also involvedin learning and memory inthe sea slug, Aplysia
Vasopressin 1a receptor correlates with partner preferences in voles
V1a receptor distribution D2 receptor distributionPartner, stranger
Meadow vole
Prairie vole
V1aR-vp Control
Control - other
Time experimental male spent huddling with partner (filled) or stranger (open) female
Eticlopride treatment(blocks dopamine receptors)
Viral-mediated transfer of V1aR alters partner preferences in voles
Lim et al. 2004 Nature
Behavior genetics referencesArnold, S.J. 1981 Behavioral variation in natural populations II. The inheritance of a feeding response in crosses between geographic races of the garter snake, Thamnophis elegans. Evolution
35:510-515.Balaban, E., M.-A. Teillet, N. LeDourain 1988 Application of the quail-chick chimera system to the study of brain development and behavior. Science 241:1339-1342.Ben-Shahar, Y., A. Robichon, M.B. Sokolowski, and G.E. Robinson 2002 Influence of gene action across different time scales on behavior. Science 296:741-744.Ben-Shahar, Y., H. T. Leung, W. L. Pak, M. B. Sokolowski, and G. E. Robinson. 2003. cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of
labor. Journal of Experimental Biology 206:2507-2515.Brandes, C., B. Frisch & R. Menzel 1988 Time-course of memory formation differs in honey bee lines selected for good and poor learning. Anim. Behav. 36:981-985.Brown, C.R. and Brown, M.B. 2000 Heritable basis for choice of group size in a colonial bird. Proc. Natl. Acad. Sci. USA 97:14825-14830.Cade, W.H. 1981 Alternative male strategies: genetic differences in crickets. Science 212:564-565.Chalfie, M. & J. Sulston 1981 Developmental genetics of the mechosensory neurons of Caenorhabditis elegans. Devel. Biol. 82:358-370.Coyne, J.A., A.P. Crittenden, K. Mah 1994 Genetics of a pheromonal difference contributing to reproductive isolation in Drosophila. Science 265:1461-1464.Dingle, H. 1994 Genetic analyses of animal migration. In: Quantitative Genetic Studies of Behavioral Evolution. pp. 145-164. (ed. C.R.B. Boake) University of Chicago Press, Chicago.Grozinger, C. M., and G. E. Robinson. 2002. Microarray analysis of pheromone-mediated gene expression in the honey bee brain. Integrative and Comparative Biology 42:1237-1237.Hall, J.C. 1979 Control of male reproductive behavior by the central nervous system of Drosophila: dissection of a courtship pathway by genetic mosaics. Genetics 92:437-457.Hall, J.C. 1994 The mating of a fly. Science 264:1702-1714.Hammock, E. A. D., and L. J. Young. 2004. Functional microsatellite polymorphism associated with divergent social structure in vole species. Molecular Biology and Evolution 21:1057-1063.Hoffman, A. 1994 Genetic analysis of territoriality in Drosophila melanogaster. In: Quantitative Genetic Studies of Behavioral Evolution. pp. 188-205. (ed. C.R.B. Boake) University of
Chicago Press, Chicago.Lim, M. M., E. A. D. Hammock, and L. J. Young. 2004. The role of vasopressin in the genetic and neural regulation of monogamy. Journal of Neuroendocrinology 16:325-332.Lim, M. M., Z. X. Wang, D. E. Olazabal, X. H. Ren, E. F. Terwilliger, and L. J. Young. 2004. Enhanced partner preference in a promiscuous species by manipulating the expression of a single
gene. Nature 429:754-757.Lim, M. M., and L. J. Young. 2004. Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole. Neuroscience 125:35-45.Krieger, M.J.B. and Ross, K.G. 2002 Identification of a major gene regulating complex social behavior. Science 295:328-332.Nol, E., K. Cheng, & C. Nichols 1996 Heritability and phenotypic correlations of behaviour and dominance rank of Japanese quail. Anim. Behav. 52:813-820.Peixoto, A.A., R. Costa, J.C. Hall 2000 Molecular and behavioral analysis of sex-linked courtship song variation in a natural population of Drosophila melanogaster. J. Neurogenetics 14:245-
256.Queller, D.C., E. Ponte, S. Bozzaro, J.E. Strassmann Science 299:105-106.Ritchie, M.G. & C.P. Kyriacou 1996 Artificial selection for a courtship signal in Drosophila melanogaster. Anim. Behav. 52:603-611.Robinson, G. E. 2002. Genomics and integrative analyses of division of labor in honeybee colonies. American Naturalist 160:S160-S172.Ross, K. G. and L. Keller 2002 Experimental conversion of colony social organization by manipulation of worker genotype composition in fire ants ( Solenopsis invicta). Behav Ecol Sociobiol
51: 287-295Ross, K.G. and L. Keller 1998 Genetic control of social organization in an ant. Proc. Natl. Acad. Sci., USA 95: 14232-14237Sakai, T. and N. Ishida 2001 Circadian rhythms of female mating activity governed by clock genes in Drosophila. PNAS 98:9221-9225.Sinvervo, B. and J. Clobert 2003 Morphs, dispersal behavior, genetic similarity, and the evolution of cooperation. Science 300:1949-1951.Stratton, G.E. & G. W. Uetz 1986 The inheritance of courtship behavior and its role as a reproductive isolating mechanism in two species of Schizocosa wolf spiders (Araneae: Lycosidae).
Evolution 40:129-141.Tang, Y. P., E. Shimizu, G. R. Dube, C. Rampon, G. A. Kerchner, M. Zhuo, G. S. Liu, and J. Z. Tsien. 1999. Genetic enhancement of learning and memory in mice. Nature 401:63-69.Takahashi, J.S., L.H. Pinto, M.H. Vitaterna 1994 Forward and reverse genetic approaches to behavior in the mouse. Science 264:1724-1733.Thomas, J.H. 1994 The mind of a worm. Science 264:1698-1699.Whitfield, C. W., A. M. Cziko, and G. E. Robinson. 2003. Gene expression profiles in the brain predict behavior in individual honey bees. Science 302:296-299.Young, L. J. 1999. Oxcytocin and vasopressin receptors and species-typical social behaviors. Hormones and Behavior 36:212-221.Young, L. J., R. Nilsen, K. G. Waymire, G. R. MacGregor, and T. R. Insel. 1999. Increased affiliative response to vasopressin in mice expressing the V-1a receptor from a monogamous vole.
Nature 400:766-768.Zhang, J. 2003 Paleomolecular biology unravels the evolutionary mystery of vertebrate UV vision. PNAS 100:8045-8047.