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

Single genes segregate: foraging

Rover is dominant: all F1 and 3:1 F2

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

Bee foraging and foraging

Ben-Shahar et al. 2002 Science

Polyethism

Drosophila courtship

Drosophila courtship mutants

Note: pleiotropy, i.e. single gene effects two or more traits

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

Chromosome locations for

human disorders

Drosophila gynandromorphs (genetic mosaics)Has been used to study where X-linked genes are expressed

during the first cell division

No vibrations Vibrations

Dark = femaleLight = male

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

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

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

cDNA microarray

analysis

What genes cause honeybees to turn into queens?

Microarrayanalysis

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