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Transcript
Single gene effects on behavior
• How do gene products affect behavior?
• What methods are used to study singlegene 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
No dominance
= additive
• 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
Complete dominance
aa
Aa
AA
Overdominance
aa
Aa
AA
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
Polyethism
Ben-Shahar et al. 2002 Science
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; indicating
1 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
Dark = female
Light = male
Vibrations
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
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 defective
adenyl-cyclase, which
forms cAMP from ATP
This pathway is also involved
in learning and memory in
the sea slug, Aplysia
dunce codes an enzyme
cAMP phosphodiesterase,
which breaks down cAMP
Cyclic AMP Response Binding protein
Creating “knock-out”
or “knock-in” mice
Vasopressin 1a receptor correlates
with partner preferences in voles
Prairie vole
Meadow vole
Partner, stranger
V1a receptor distribution
D2 receptor distribution
Viral-mediated transfer of V1aR
alters partner preferences in voles
V1aR-vp
Control
Control - other
Eticlopride treatment
(blocks dopamine receptors)
Time experimental male spent
huddling with partner (filled)
or stranger (open) female
Lim et al. 2004 Nature
cDNA
microarray
analysis
What genes cause honeybees to
turn into queens?
Microarray
analysis
Behavior genetics references
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