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Transcript
大學部 生態學與保育生物學學程 (必選)
2010 年 秋冬
基因分析(Genetic analysis)
─動物行為學 (Ethology)
鄭先祐(Ayo)
國立 臺南大學 環境與生態學院
生態科學與技術學系 教授
Ayo NUTN Web: http://myweb.nutn.edu.tw/~hycheng/
Part 1. 動物行為的研究途徑 (個體行為)
 歷史背景 (History of the Study of Animal




Behavior ).
基因分析 (Genetic Analysis of Behavior ).
天擇 (Natural Selection and Behavior ).
學習與認知 (Learning and Cognition.)
生理分析 (Physiological Analysis)


(一) 神經細胞 (Nerve Cells and Behavior ).
(二) 內分泌系統 (The Endocrine System).
 發育(The Development of Behavior ).
Ayo 教材 (動物行為學 2010)
2
03 基因分析(Genetic analysis)
 Basic of Gene Action
 行為遺傳學 (Behavioral Genetics)



Goals and Methods
Example: The Foraging Gene
Important principles
 Behavioral Variation and Genes
 Environmental Regulation of Gene Expression
Ayo 教材 (動物行為學 2010)
3
基因、經驗 與 行為
 Behavior is determined by gene activity
 For example, it influences how adult rats respond to stress
and how attentive females will be to their pups
 This change in gene activity is transmitted to the next
generation
 Behavior is also determined by early experience
 The mother of calm rat pups spends a lot of time grooming
and nursing them
Ayo 教材 (動物行為學 2010)
4
The quality of maternal care affect the pups’ responses to
stress, now and in adulthood
Ayo 教材 (動物行為學 2010)
5
基因與行為的關係
 Genes and behavior do not exist in a one-to-one
correspondence



For example: a fly’s eating behavior involves many sense
organs, neurons and muscles
The structure and function of each of these pieces is
influenced by many genes
Behavior is also influenced by the animal’s internal
physiological state and the external environment
 An animal’s actions result from many genes interacting
with one another and the environment
Ayo 教材 (動物行為學 2010)
6
行為遺傳學 (behavioral genetics)
Goals:
 to identify the gene, or genes, that underlie a
behavior

And to learn the functions of these genes
 to decipher the interactions among genes and their
products


And between genes and the environment
How much behavioral variation is due to genetic
differences and how much is caused by the
environment
Ayo 教材 (動物行為學 2010)
7
Heritability is a statistical measure
 The heritability of a trait in a population is the ratio of
the variation caused by genetic differences to the total
amount of variability in the trait



Varies from 0 to 1
A value of 0.5 = 50% of the variability in the population is
due to genetic differences
The heritability of a complex trait such as behavior is
rarely more than 50%
Ayo 教材 (動物行為學 2010)
8
Genomics (基因組學)
 Genomics (基因組學): the study of an organism’s
entire genome (DNA)

patterns of genome activity under different conditions
or at different developmental stages
 Comparative genomics (比較基因組學) compares
and analyzes the genomes of different species

to understand how species have evolved
 Proteomics (蛋白質組學):the full set of proteins
coded for by an organism’s genes
Ayo 教材 (動物行為學 2010)
9
行為遺傳學的方法
 找出與行為相關的基因。
 培育inbred strains,
 運用 cross inbred
 驗證各個基因的行為功能。
 運用各種不同的情境或環境狀態。


Cross-fostering
擁有不同基因個體,於相同情境或環境,行為有何
差異?
Ayo 教材 (動物行為學 2010)
10
案例:蓋斑鬥魚的抗掠食行為
(Antipredator behavior)
 Avoiding predation is crucial to survival, and has a
genetic basis
 Researchers measured the responses of the larvae of two
inbred strains (S and P) to model predators

The larvae of strain P showed more antipredator
responses than the larvae of strain S
Ayo 教材 (動物行為學 2010)
11
蓋斑鬥魚 (paradise fish)
 蓋斑鬥魚是一種小型的淡水
魚類,又名三斑鬥魚、台灣
鬥魚,香港稱之為叉尾鬥魚。
英文名稱為天堂魚(Paradise
fish),日本人稱台灣金魚。
原產於中國南部、海南島、
中南半島及台灣。
 This species lives in marshes
and rice fields in Southeast
Asia
Ayo 教材 (動物行為學 2010)
12
Cross-fostering determines maternal influences
 Cross-fostering: transferring the offspring shortly
after birth to a mother of a different strain


Can detect maternal influences that occur after birth
When offspring transferred to a foster mother
immediately after birth behave like individuals of the
foster mother’s strain
Ayo 教材 (動物行為學 2010)
13
案例:Cross-fostering voles
 Prairie voles(草原田鼠) show more parental care than
meadow voles (草地田鼠)

Females and males spend more time with their young,
huddling over them and nursing them
 To determine whether the species difference in parental
care was due to genes or early experience, meadow vole
pups were fostered to prairie vole parents
Ayo 教材 (動物行為學 2010)
14
Meadow Vole(草地田鼠) vs. Prairie Vole
(草原田鼠)
 The Meadow Vole (Microtus pennsylvanicus) is a small North American
vole found across Canada, Alaska and the northern United States. Its
range extends further south along the Atlantic coast.
 The Prairie Vole (Microtus ochrogaster) is a small vole found in central
North America.
Ayo 教材 (動物行為學 2010)
15
嬰兒期的影響
 When the foster pups had their own families
 Meadow vole pups raised by prairie voles cared more
for their offspring
 Nonsocial behaviors (i.e. food caching and tunnel
building) were not modified by early experience
Ayo 教材 (動物行為學 2010)
16
基因與環境:adoption studies
 Siblings adopted into different families
 The degree of similarity between siblings show the
contribution of genes to the family resemblance
 When families with children adopt additional children
 Children with different genetic backgrounds live in the same
environment
 The degree to which the family’s own children resemble the
adopted children indicates environmental
 In adoption-twin studies, twins adopted into different
families are compared to twins raised in the same family
Ayo 教材 (動物行為學 2010)
17
Artificial selection (人擇) can create breeds
 In a genetically variable population, individuals who show
the desired attribute are mated


If the trait has a genetic basis, the alleles responsible for it
increase in frequency
The behavior becomes more common or exaggerated
 The frequency of particular behavior patterns present in all
breeds has been modified through artificial selection
Ayo 教材 (動物行為學 2010)
18
案例:Artificial selection for nesting
behavior
 Nesting behavior in house mice has a genetic basis
 Natural selection might work on the trait in wild
populations
 House mice live in fields, and build nests of soft plant
material

Lab mice, both males and females, use cotton as nesting
material
Ayo 教材 (動物行為學 2010)
19
Mouse nest size
 Mice were selectively
mated, based on the size
of the nest they built
 After generations of
artificial selection,
large-nesting mice
collected more cotton
than mice of the small
nesting line
Some mice build larger
nests than others
Ayo 教材 (動物行為學 2010)
20
Mouse nest size
Ayo 教材 (動物行為學 2010)
21
Nest size influences fitness
 Natural selection could influence nest building if nest size
influences fitness (the number of offspring successfully raised)
 House mice build larger nests in the north than in the south.
Large nests may help mice in cold environments raise more
offspring
 Mice from the lines that built larger nests raised more pups that
lived to be 40 days old at lower temperatures
 Nest building is an important component of fitness, and its genetic
basis allows it to be shaped by natural selection
Ayo 教材 (動物行為學 2010)
22
Mutations can screen for changes in
behavior
 Agents that change the DNA bases can cause a
mutation
 Genetic crosses determine if the behavioral change is
caused by an alteration in a single gene


Even a small change can change an anatomical
structure or a physiological process that mediates a
behavior
Identifying these differences helps us understand how
genes influence behavior
Ayo 教材 (動物行為學 2010)
23
案例:Dunce fruit flies (果蠅) are poor
learners
 Odors are important for locating food and appropriate
mates

Normal fruit flies that associate an odor with an unpleasant
event (i.e. an electric shock) learn to avoid that odor
 Exposing flies to a mutation-causing chemical caused the
dunce mutation


Dunce fruit flies have a normal sensory system: they can
detect both odors and an electric shock
But they can’t remember the association between the shock
and an odor

An early stage of memory formation is defective
Ayo 教材 (動物行為學 2010)
24
Mutations affect cAMP levels
 cAMP (cyclic AMP) is a mediator of many processes in
different types of cells

It is involved in memory formation
 Dunce and rutabaga mutations have opposite effects on
the level of cAMP within a cell
 The dunce mutation reduces an enzyme that breaks
down cAMP

cAMP levels increase
 The rutabaga mutation reduces a different enzyme
 cAMP levels decrease
Ayo 教材 (動物行為學 2010)
25
cAMP and memory formation
 cAMP activates the PKA enzyme
Which activates the CREB
gene
 Which codes for the protein
CREB that activates other
genes
 These other genes control the
growth of connections between
brain cells
 Changes in the nervous system
that are responsible for
memory

Ayo 教材 (動物行為學 2010)
26
案例: Feeding behavior in larval fruit
flies (果蠅)
 Two forms of feeding behavior occur in natural
populations of larval fruit flies

“Rover” larvae move around continually on their food


They leave their food source to look for another
“Sitter” larvae travel only short distances

They remain on a food source
 When food is not present all flies move rapidly, as
rovers do

Sitters are not energy-deficient or sick
Ayo 教材 (動物行為學 2010)
27
The genetic basis of foraging strategies
 To investigate the genetic basis of fruit fly foraging
strategies, rovers and sitters were mated


The “hybrid” offspring were compared to pure rovers
and pure sitters
The path lengths of rovers differ from that of sitters
Ayo 教材 (動物行為學 2010)
28
 The result of mating
experiments on fruit
flies showing “rover”
or “sitter” foraging
strategies as larvae.
Ayo 教材 (動物行為學 2010)
29
The foraging (for) gene
 A single foraging (for) gene causes variation in foraging strategies
of larval fruit flies
 For is located close to a gene for the enzyme PKG
 PKG is important in signaling pathways within the cell
 The for gene is identical to the gene that produces PKG
 Adult rover flies had more PKG than adult sitter flies
 PKG causes differences in behavior
 Over the course of evolution, DNA sequences that influence a
particular behavior tend to be conserved between species
 The for gene affects food-related behaviors in other species
Ayo 教材 (動物行為學 2010)
30
Candidate genes (候選基因)
 Candidate genes: genes that might be involved in the
trait in question

Are based on their location or their role in other
organisms
 For is a candidate gene for foraging behavior
Ayo 教材 (動物行為學 2010)
31
 The candidate
gene approach.
Ayo 教材 (動物行為學 2010)
32
物種分享基因
 Genes similar to the for gene occur in other organisms
 Honeybees
 Red harvester ants
 Nematodes
 The versions of for in these species affect the level of PKG
 The genes are orthologues - they descended from the same
ancestral gene and have the same function
 But, for and PKG affects foraging through different
mechanisms and may be regulated differently in species
Ayo 教材 (動物行為學 2010)
33
Foraging behavior in
different species
When the foraging gene is
expressed, PKG levels
increase, changing foodrelated behavior in
several species
Ayo 教材 (動物行為學 2010)
34
The importance of genetic background
 In the fruit fly rover vs. sitter
 Increased cGMP increases PKG levels and rover
foraging behavior
 A mutation in a gene other than for that decreases
cGMP should also decrease PKG and locomotion
during foraging


This did not happen
The mutation’s effect on the pattern of gene expression
depended on whether the fly’s genotype was rover or
sitter
Ayo 教材 (動物行為學 2010)
35
案例:Honeybee foraging
 Fruit flies forage to satisfy their own hunger, but honeybee
workers forage to bring food back to their colony

Their own hunger is not lessened by foraging
 A honeybee’s duties depend on her age
 After emerging from its brood cell, a bee cleans the cells
 She becomes a “nurse,” caring for and feeding the brood
 When she is 2 or 3 weeks old, she becomes a forager

Leaving the hive to collect pollen or nectar
Ayo 教材 (動物行為學 2010)
36
A honeybee’s duties depend on the
for gene
 The age-related switches are associated with increased
activity of the for gene in the brain
 Increased for activity
 Increases the for mRNA level
 Which encodes PKG
Ayo 教材 (動物行為學 2010)
37
Levels of for
mRNA in the
brain are higher
in foragers than
in nurses
The foraging gene become active as nurse honeybees leave the hive and become
foragers.
Ayo 教材 (動物行為學 2010)
38
案例: For affects behavior of red
harvester ants
 Red harvester ants live in large colonies
 Some ants work inside the colony (i.e. caring for newly
emerged ants) Others forage outside the colony
 For varies as workers switch from within-colony duties
to foraging
 The relationship between for expression and behavior is
the opposite of honey bees

For expression is greater in workers in the colony than in
foragers
Ayo 教材 (動物行為學 2010)
39
案例: For affects nematode (線蟲) foraging
 The nematode (roundworm) has two forms of foraging:
 A roamer travels long distances without stopping
 A dweller travels short distances and makes frequent
stops
 Differences in the alleles of the for gene result in
roaming or dwelling during foraging

Unlike fruit flies, where roving increases with for gene
activity, roaming decreases with for gene activity
Ayo 教材 (動物行為學 2010)
40
Gene expression can be changed
 Adding copies (knocking in) of the gene increases
activity

Increases protein, causing a greater effect on behavior
 Disabling (knocking out) genes decreases gene activity
 Eliminates the product of the disabled gene
 If the behavior is changed by altering the activity of the
gene

The gene is involved in producing that behavior
Ayo 教材 (動物行為學 2010)
41
Gene expression can be changed
 Adding extra copies of for increased PKG levels in
sitter flies

Sitter foraging behavior was similar to rover flies
 Knocking out the nematode for gene increased
roaming behavior
Ayo 教材 (動物行為學 2010)
42
Many genes affect a trait
 The expression of most behaviors varies because many
genes play a role in shaping behavior
 A quantitative trait involves many genes

A quantitative trait locus (QTL): a region of DNA
associated with a particular quantitative trait
 A goal of QTL research: to identify the many genes
underlying a trait and the extent to which each alters the
trait

Comparing a QTL to a database of genes whose functions
are known can identify candidate genes
Ayo 教材 (動物行為學 2010)
43
案例: Behaviors involved in honeybee
foraging
 A forager has many “decisions” to make, including the
type of food it obtains
 Four genes (“pollen” QTLs) underlie foraging
behaviors

Each of these genes plays a very specific role in the
behavior of pollen collection
Ayo 教材 (動物行為學 2010)
44
Microarray analysis
 Not all genes are expressed (active) during a behavior
 Microarray analysis: investigates the effect of many
genes on a behavior

Creates a gene expression profile by monitoring the
expression of hundreds or even thousands of genes at
once

Ayo 教材 (動物行為學 2010)
45
 A DNA microarray: thousands of DNA sequences
stamped onto a solid surface, such as a glass slide


Molecular tags identify mRNA produced by each gene
Greater mRNA production increases gene activity
 Genes that are active only during a particular behavior
may play a role in producing that behavior
Ayo 教材 (動物行為學 2010)
46
Gene expressions in bees
 Patterns of gene expression in nurse bees (5 to 9 days
old) and forager bees (28 to 32 days old) showed
significant differences in the expression of many genes
 The gene expression patterns reflect the bee’s behavior,
not its age
 The gene expression profile in the brain of a honeybee
nurse differs from that of the forager brain, even if the
nurse and forager are the same age.
Ayo 教材 (動物行為學 2010)
47
One gene can affect several traits
 The honeybee for gene is regulated by vitellogenin, the
protein product of the vitellogenin gene


Affects social organization and foraging through multiple
(pleiotropic) effects
Its level declines with age, allowing the transition to
forager
 Pollen collectors have high levels earlier in life
Ayo 教材 (動物行為學 2010)
48
Ayo 教材 (動物行為學 2010)
49
RNA interference lowers vitellogenin
 RNAi (RNA interference) lowers the mRNA
produced by the vitellogenin gene
 With lower vitellogenin levels



Worker honey bees switch from nurse to forager
earlier
Prefer nectar as a food source
Live shorter lives
Ayo 教材 (動物行為學 2010)
50
Genes work in interacting networks
 Genes work in functional networks, which interact to
form genetic modules (基因模組) that are responsible
for a certain behavior

The genetic modules have overlapping regions
 A change in a single gene can cause a change that has
a ripple effect (漣漪效應)

That causes changes in interacting gene modules and
affect many related traits or behaviors
Ayo 教材 (動物行為學 2010)
51
A diagram of overlapping genetic modules.
 Each circle: a genetic module
that controls a specific behavior

The arrows show mRNA
transcripts that affect a genetic
module
 Gene module 1 affects itself
and gene modules 2 and 3

Gene module 1 affects gene
module 5 through its effects on
gene module 3
Ayo 教材 (動物行為學 2010)
52
Genes and social bonds in rodents
 For example: four genes interact in forming social bonds
in rodents
 The protein products of these four genes are:


Estrogen receptors α and β, oxytocin, and its receptor
Estrogen and oxytocin are hormones: chemical messengers
carried through the body
 Interactions of all four genes are needed for social bonding
to occur

If even one of the genes was disabled, mutant mice can’t
distinguish a familiar mouse from a stranger
Ayo 教材 (動物行為學 2010)
53
The olefactory basis of social recognition
 Olfactory cues are detected by sensory receptors
 Estrogen binds to estrogen receptor β and turns on the
oxytocin gene
 Oxytocin binds to estrogen receptor , and turns on
oxytocin receptor genes
 Enabling social recognition
 Disrupting this gene micronet causes the entire
system to fail
Ayo 教材 (動物行為學 2010)
54
 A diagram of a four-
gene micronet
underlying social
recognition.
Ayo 教材 (動物行為學 2010)
55
Behavioral variation and genes
 Genetically-controlled behavior is not necessarily fixed
It can be dynamic and responsive to the environment
 Behavioral variation could result from differences in gene
regulation
 Changing conditions in a tissue changes gene activity
 New genes will be turned on, other genes will be turned
off
 The level of expression of a gene can also be modified
 Regulatory regions of DNA control gene activity

Ayo 教材 (動物行為學 2010)
56
Spatial differences in gene expression
 Spatial differences in gene expression cause prairie
voles to be monogamous (一夫一妻)

Male meadow voles are not
 Both species produce the hormone vasopressin and
have vasopressin receptors
Ayo 教材 (動物行為學 2010)
57
 Social bond formation and vasopressin receptor
distribution.
Ayo 教材 (動物行為學 2010)
58
Vasopressin (血管增壓素)
 Genetic variation in the vasopressin receptor gene
underlies the distribution of vasopressin receptors

Vasopressin receptors are concentrated in a reward system
of the brain
 Male prairie voles have many vasopressin receptors
 After mating, the feeling of reward caused by vasopressin
results in a pair bond with the female
 Male meadow voles have few vasopressin receptors
 The reward system is not stimulated and no pair bond
forms
Ayo 教材 (動物行為學 2010)
59
Stop and think
 Before identifying the vasopressin receptor
distribution as the cause of the difference in social
bonding in monogamous prairie voles and in nonmonogamous montane voles, researchers injected
vasopressin into the brains of both prairie voles and
montane voles


Why was this step necessary?
What outcome led the researchers to conclude that the
distribution of receptors was the critical difference
between the responses of these species?
Ayo 教材 (動物行為學 2010)
60
Hormones affect human social behavior
 Hormones affect human social behavior, including autism (自閉
症)
Autism is characterized by poor communication and social
skills
 Are alterations in the oxytocin or vasopressin signaling pathways
related to autism?
 Oxytocin and vasopressin levels are lower in autistic children
 Oxytocin administration boosts some social skills in autistic
patients
 Also, variation in the vasopressin receptor promoter gene is
associated with autism

Ayo 教材 (動物行為學 2010)
61
Nature and nurture (本質和培育)
 Heritability (遺傳性) : the part of the variation in a
trait attributed to genetics

The remaining variability is due to the environment
 Behavior: product of genes and environment acting on
the genome

Nature and nurture
 Change in the pattern of gene expression shows this
interaction
Ayo 教材 (動物行為學 2010)
62
 Genes and the
environment
interact to
produce
behavior.
Ayo 教材 (動物行為學 2010)
63
案例: Dominance relationships in cichlid fish
(慈鯛魚類)
 Two types of males in the cichlid fish
 Dominant males: brightly colored, aggressive, and
have greater reproductive success
 Subordinate males: non-territorial, have camouflage
coloration, are less likely to be chosen as mates
 The physical environment of the habitat fluctuates,
causing frequent changes in dominance relationships

As a male rises in social status, he becomes sexually
mature and his growth rate slows
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 Cichlids慈鯛科,又稱麗魚科,為輻鰭魚綱鱸形目的
其中一科,已知約200個屬,超過2000種,是硬骨魚
類中的大家族。The family Cichlidae is both large and
diverse.
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GnRH in cichlid fish
 The GnRH gene codes for gonadotropin-releasing hormone
(GnRH)
 Dominant males have increased activity of the GnRH gene
 The GnRH gene is regulated by social stimuli resulting from
dominance or submission
 GnRH gene activity and the number of receptors increase
 When a non-territorial male wins aggressive encounters
 GnRH triggers the release of sex hormones (gonadotropins)
 Testes develop and sperm is produced
 GnRH causes him to change color from gray to blue or yellow
 Signals to both male and female fish that he is dominant
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Body size is also affected by social status
 Body size allows a male to attain dominance
Subordinate males grow faster than dominant males
 With dominance, growth rate slows and energy goes to
reproduction
 Social stimuli increase expression of a gene encoding the hormone
somatostatin
 Somatostatin inhibits the release of growth hormone (GH)
 Leading to slower growth
 If he becomes subordinate, somatostatin levels decrease and GH
levels increase, increasing his growth rate again

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A rise in social status may occur rapidly
 Within minutes of the opportunity to rise in social status, the
subordinate male changes
 He becomes brilliantly colored, makes threatening displays and
chases other males
 Activity of the immediate early gene, erg-1, increases
 It codes for proteins that regulate the activity of other genes,
including GnRH
 The protein product of GnRH increases sex hormone levels
 Erg-1 also activates other genes that produce proteins important in
the growth and activity of nerve cells
 Which underlie behavioral changes
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案例:Song learning in male songbirds
 A young male bird learns to sing his species song by
imitating adult males

Territory defense and mate attraction
 Immediate-early genes become active after a nerve cell
is stimulated

They code for proteins that regulate the activity of other
genes. Other genes produce proteins for nerve cell growth
and activity

Zenk is one of these genes
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金絲雀
 Zenk gene activity in the forebrains of male songbirds
following exposure to songs of their own species, songs of
another species, bursts of tones that are not song, or no
auditory stimulation.
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斑胸草雀
 Zenk gene activity in the forebrains of male songbirds following exposure
to songs of their own species, songs of another species, bursts of tones
that are not song, or no auditory stimulation.
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The zenk gene
 When a male songbird hears its species’ song
 Levels of zenk mRNA rise
 Zenk activity increases
 Zenk activity
 Underlies formation of long-term memories and
 Increases in response to the songs of unfamiliar males
and
 Is higher in males whose territories are challenged
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 第一次 2.5小
時,接著第二
次(test
stimulus)30分
鐘。
 Zenk activity in auditory regions of the forebrain of a
male zebra finch drops following repeated exposure to
the song of one male, but it can be reactivated by a new
song.
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案例:Atlantic salmon(大西洋鮭魚)
 A different subset of genes is expressed in sneaker and
immature male Atlantic salmon
 Sneakers: small males that steal matings

Active genes are associated with reproduction
 Other males migrate out to sea, mature, and return years
later

Active genes are associated with growth
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 Proportion of
genes with
increased
activity in (a)
sneaker male
and (b)
immature
male Atlantic
salmon.
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Epigenetics and behavioral genetics
 Epigenetics: involves a stable alteration in gene
expression without changes in DNA sequence

They regulate how genes are expressed but don’t
change the proteins they encode
 Epigenetic processes— such as DNA methylation
and histone acetylation—can influence behavior

They alter gene expression by affecting how tightly
packaged the DNA molecule is.
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DNA can be less or more tightly coiled
 DNA methylation(甲基化) (adding a methyl group)
turns off the activity of a gene



It brings in proteins that compact DNA
Reducing access by regulatory proteins that promote
transcription
Is dynamic and changes over time
 Histone acetylation (乙醯化) makes the DNA less
tightly coiled and gene expression easier
 These processes can be affected by the environment
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Maternal care affects stress responses
 Some Norway rat mothers nurture young more than other
mothers

Their pups tolerate stress better than pups of less attentive
mothers
 Glucocorticoids: hormones released in response to stress
 Frequent contact with pups increases the expression of a
gene for a glucocorticoid receptor in the brain

They are less fearful
 Neglected pups have fewer glucocorticoid receptors
 They are anxious and fearful in response to stress
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Chromosome changes affect gene regulation
 Changes in chromosome structure cause changes in
gene regulation which cause differences in maternal
care and response to stress
 At birth the promoter region of the glucocorticoid
receptors of pups is demethylated (去甲基化)

At the end of the first day, the promoter region begins
methylation
 The promoter region of a glucocorticoid receptor in the
pups of neglectful mothers was more methylated
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Serotonin and stress reduction
 Licking and grooming increases the level of serotonin
 Serotonin increases expression of the NGFI-A gene
 Increasing the amount of a protein called NGFI-A
 This protein binds to the glucocorticoid receptor gene and
attracts two enzymes

Both make DNA less tightly coiled and more easily expressed
 The increased expression increases the number of
glucocorticoid receptors

And lessens the pups’ responses to stress
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血清張力素 (Serotonin)
 血清張力素,又稱血清素、
5-羥色胺,為單胺型神經
遞質,由色胺酸衍生而來,
合成於中樞神經(CNS)元
及動物(包含人類)消化
道之腸嗜鉻細胞內。
 許多蘑菇與植物(含蔬果)
中皆含有血清素。
 研究指出,血清素和強迫
症以及戀愛有密切關係。
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Mother-pup interactions cause stable genetic
changes
 Maternal care also influences how nurturing a female pup
will be toward her own young when she becomes an adult
 The effect on future mothering results from epigenetic
changes in a gene
 Poor maternal care results in methylation of genes for
receptors of Glucocorticoid hormone, which mediates
stress responses

Genes for an estrogen receptor (ER ), which is needed for
proper response to oxytocin (催產素)

Oxytocin is a hormone crucial for maternal care
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 催產素(Oxytocin,或催生素)是一種荷爾蒙
(又譯激素)。可以在大腦裡自然產生, 有控制
雌性哺乳動物乳汁分泌的作用。
 由下視丘之視旁核製造,經下視丘腦下垂體路徑
神經纖維送到後葉分泌。
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Stop and think
 Pups of mother rats who offered poor maternal care were
cross-fostered to mothers who offered good maternal
care



Pups from good mothers were cross-fostered to mothers
who offered poor maternal care
As adults, the pups raised by good mothers handled stress
well, and the females were good mothers
The pups raised by poor mothers were fearful as adults
and the females were poor mothers
 Why were these experiments necessary?
 What can you conclude from them?
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Methylation can be reversed in adulthood
 Pups who had received poor maternal care became
less fearful and better mothers when injected with
trichostatin A, which causes demethylation
 The effects of good maternal care can also be
reversed
 Methionine (蛋氨酸) , found in the diet, can add a
methyl group to DNA

Adult offspring became anxious in stressful situations
and the females showed little maternal care
 Methylation patterns can be affected by the
environment, cause disease, and be transmitted
through generations and influence evolution
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 Trichostatin A (TSA) is an organic compound that
serves as an antifungal antibiotic and selectively
inhibits the class I and II mammalian histone
deacetylase (HDAC) families of enzymes.


TSA inhibits the eukaryotic cell cycle during the
beginning of the growth stage.
TSA can be used to alter gene expression by interfering
with the removal of acetyl groups from histones (histone
deacetylases, HDAC) and therefore altering the ability
of DNA transcription factors to access the DNA
molecules inside chromatin.
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案例:Vinclozoin exposure in rats
 Vinclozolin: a fungicide that is an environmental endocrine
disrupter
 It interferes with hormone signaling
 Changes the methylation pattern of rat genes, including
regulatory regions of DNA, reducing gene expression
 Exposed rat embryos have more diseases and lower fertility
 Risks are passed through four generations, even if the offspring
have never been in contact with vinclozolin
 Female rats shows a significant preference for unexposed males
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 Vinclozolin (免克寧) is a common dicarboximide
fungicide used in vineyards. It is a known endocrine
disruptor.
 Recent scientific findings have shown that exposure in
rats can lead to alterations in DNA that last for four
generations. These observations, however, should be
viewed with caution as they were not confirmed in a
larger study over three generations.
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Epigenetic changes in DNA and learning
 Rats conditioned to be fearful of a location froze
when they were placed in the chamber at a later time

They had formed fearful memories of the chamber
 The pattern of DNA methylation in the brain changes
when memories are formed
 As fearful memories form there is rapid


Methylation (silencing) of a memory-suppressing gene
and
Demethylation of a memory-promoting gene reelin
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The role of epigenetics and disease
 Epigenetics may play a role in human behavioral
disorders

I.e. developmental disorders, inherited forms of mental
impairment
 DNA is sensitive to the environment
 Our diet and chemical exposure may influence our health
by affecting our gene expression patterns
 The lifestyle of a person’s ancestors, and not just the
individual’s behavior, can influence health
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 Maternal nutrition
during pregnancy causes
epigenetic changes in
gene activity in the fetus
that increases its
susceptibility to a wide
variety of diseases
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A new interdisciplinary field
 Evolutionary and ecological functional genomics:
a new interdisciplinary field


Studies the processes that are biologically important to
both adaptation to the environment and evolutionary
fitness
Investigates how the mechanisms underlying a
behavior increase function in a natural environment to
increase evolutionary fitness
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Behavioral ecologists
 Individuals have polymorphisms: slight differences in
genes


That produce subtle differences in phenotype on which
natural selection can act
Microarray analysis identifies genes whose activity is
correlated with important ecological conditions
 Examples of ecological genomics include:
 Social recognition, dominance relations, monogamy vs.
polygamy, and alternative reproductive strategies
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Genome sequences
 Polymorphisms in a natural population may result in
subtle changes in the way in which genes interact



Giving rise to differences in the trait (behavior)
During evolution, natural selection “selects” genetic
polymorphisms that result in changes in the trait
For example, finches on the Galapagos Islands have
different beak shapes and sizes - adaptations to different
food types
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Evolutionary functional genetics
 Focuses on genomics and evolution
 Evolution can occur by selection of new alleles or by
gene regulation
 A relationship between a signaling molecule (PKG)
and a behavior (obtaining food) can be conserved in
evolution
 An association can evolve more than once

Increased levels of PKG have the opposite effect on
behavior in fruit flies and honeybees as they do in
harvester ants and nematodes
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Socio-genomics
 Evolutionary and ecological functional genomics applies
to sociality
 Sociogenomics: examines interactions among members
of the same species
 Tries to understand how genes influence social behavior


Involves identifying and understanding the functions of
genes
Studies how genes affect the mechanisms that bring about
behavior, primarily those of the nervous and endocrine
systems
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 Complex
relationships
among genes,
the nervous
system, and
behavior
occur over
different time
scales.
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Summary
 Behavior depends on which genes, made of DNA, are




being expressed, when, and in which tissues
Behavioral genetics deciphers the interactions among
genes and between genes and the environment
Inbreeding, artificial selection, and hybridization
demonstrates the genetic basis of behavior
One gene can affect several traits and can work in
interacting networks
Immediate early genes indicate the interactions of genes
with the environment
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Summary
 Changes in the tightness of the coiling of DNA
influence gene expression without altering the DNA
sequence
 Evolutionary and ecological evolution examines how
natural selection selects genes responsible for
ecologically adaptive behavior
 Sociogenomics is the evolutionary and ecological
genomics of social behavior
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問題與討論
[email protected]
 Ayo 台南 NUTN 站
http://myweb.nutn.edu.tw/~hycheng/
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