Single gene effects on behavior

1. 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

2. 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?

3. 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

4. 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

5. 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)

6. Phenotype No dominance = additive aa Aa AA Phenotype aa Aa AA Phenotype Overdominance aa Aa AA 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 Complete dominance

7. Single genes segregate: foraging Rover is dominant: all F1 and 3:1 F2

8. 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

9. Bee foraging and foraging Polyethism Ben-Shahar et al. 2002 Science

10. Drosophila courtship

11. Drosophila courtship mutants Note: pleiotropy, i.e. single gene effects two or more traits

13. 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

14. RFLP association with Huntington’s chorea Note that 33 of 34 affected individuals have the C allele; indicating 1 recombination event and tight linkage between C and HD genes

15. Chromosome locations for human disorders

16. Drosophila gynandromorphs (genetic mosaics) Has been used to study where X-linked genes are expressed during the first cell division

17. No vibrations Vibrations Dark = female Light = male

18. 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 conspecific period genes. Cross species transformations with per altered male behavior to approximate the other species. Epistasis - genetic background affects behavior

19. 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

20. Memory formation in flies dunce codes an enzyme cAMP phosphodiesterase, which breaks down cAMP rutabaga has defective adenyl-cyclase, which forms cAMP from ATP This pathway is also involved in learning and memory in the sea slug, Aplysia Cyclic AMP Response Binding protein

21. Creating “knock-out” or “knock-in” mice

22. Vasopressin 1a receptor correlates with partner preferences in voles Prairie vole Meadow vole Partner, stranger V1a receptor distribution D2 receptor distribution

23. V1aR-vp Control Control - other Eticlopride treatment (blocks dopamine receptors) Viral-mediated transfer of V1aR alters partner preferences in voles Time experimental male spent huddling with partner (filled) or stranger (open) female Lim et al. 2004 Nature

24. cDNA microarrayanalysis

25. What genes cause honeybees to turn into queens?

26. Microarrayanalysis

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