基因分析 (Genetic analysis) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立 臺南大學...

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基基基基 (Genetic analysis) 基基基基基 (Ethology) 鄭鄭鄭 (Ayo) 鄭鄭 鄭鄭鄭鄭 鄭鄭鄭鄭鄭鄭鄭 鄭鄭鄭鄭鄭鄭鄭鄭鄭 鄭鄭 Ayo NUTN Web: http:// myweb.nutn.edu.tw/~hycheng / 鄭鄭鄭 鄭鄭鄭鄭鄭鄭鄭鄭鄭鄭鄭 ( 鄭鄭 ) 2010 鄭 鄭鄭

Transcript of 基因分析 (Genetic analysis) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立 臺南大學...

Page 1: 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: hycheng/ hycheng

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/

大學部 生態學與保育生物學學程 ( 必選 ) 2010 年 秋冬

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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 ).

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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

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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

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The quality of maternal care affect the pups’ responses to stress, now and in adulthood

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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

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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

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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%

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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

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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?

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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

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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

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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

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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

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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.

Page 16: 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: hycheng/ hycheng

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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

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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

Page 18: 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: hycheng/ hycheng

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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

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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

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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

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Mouse nest size

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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

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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

Page 24: 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: hycheng/ hycheng

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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

Page 25: 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: hycheng/ hycheng

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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

Page 26: 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: hycheng/ hycheng

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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

Page 27: 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: hycheng/ hycheng

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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

Page 28: 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: hycheng/ hycheng

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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

Page 29: 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: hycheng/ hycheng

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The result of mating experiments on fruit flies showing “rover” or “sitter” foraging strategies as larvae.

Page 30: 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: hycheng/ hycheng

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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

Page 31: 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: hycheng/ hycheng

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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

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The candidate gene approach.

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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

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Foraging behavior in different species

When the foraging gene is expressed, PKG levels increase, changing food-related behavior in several species

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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

Page 36: 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: hycheng/ hycheng

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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

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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

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The foraging gene become active as nurse honeybees leave the hive and become foragers.

Levels of for mRNA in the brain are higher in foragers than in nurses

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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

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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

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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

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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

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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

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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

Page 45: 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: hycheng/ hycheng

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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A diagram of a four-gene micronet underlying social recognition.

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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

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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

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Social bond formation and vasopressin receptor distribution.

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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

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Stop and think

Before identifying the vasopressin receptor distribution as the cause of the difference in social bonding in monogamous prairie voles and in non-monogamous 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?

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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

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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

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Genes and the environment interact to produce behavior.

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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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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.

金絲雀

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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.

斑胸草雀

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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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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.

第一次 2.5 小時,接著第二次 (test stimulus)30 分鐘。

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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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Ayo 台南 NUTN 站 http://myweb.nutn.edu.tw/~hycheng/