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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 Ayo 教材 (動物行為學 2010) 64 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. Ayo 教材 (動物行為學 2010) 65 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 Ayo 教材 (動物行為學 2010) 66 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 Ayo 教材 (動物行為學 2010) 67 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 Ayo 教材 (動物行為學 2010) 68 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 Ayo 教材 (動物行為學 2010) 69 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. Ayo 教材 (動物行為學 2010) 70 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. Ayo 教材 (動物行為學 2010) 71 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 Ayo 教材 (動物行為學 2010) 72 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. Ayo 教材 (動物行為學 2010) 73 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 Ayo 教材 (動物行為學 2010) 74 Proportion of genes with increased activity in (a) sneaker male and (b) immature male Atlantic salmon. Ayo 教材 (動物行為學 2010) 75 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. Ayo 教材 (動物行為學 2010) 76 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 Ayo 教材 (動物行為學 2010) 77 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 Ayo 教材 (動物行為學 2010) 78 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 Ayo 教材 (動物行為學 2010) 79 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 Ayo 教材 (動物行為學 2010) 80 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。 Ayo 教材 (動物行為學 2010) 81 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 Ayo 教材 (動物行為學 2010) 82 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。 Ayo 教材 (動物行為學 2010) 83 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? Ayo 教材 (動物行為學 2010) 84 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 Ayo 教材 (動物行為學 2010) 85 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. Ayo 教材 (動物行為學 2010) 86 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 Ayo 教材 (動物行為學 2010) 87 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. Ayo 教材 (動物行為學 2010) 88 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 Ayo 教材 (動物行為學 2010) 89 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 Ayo 教材 (動物行為學 2010) 90 Maternal nutrition during pregnancy causes epigenetic changes in gene activity in the fetus that increases its susceptibility to a wide variety of diseases Ayo 教材 (動物行為學 2010) 91 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 Ayo 教材 (動物行為學 2010) 92 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 Ayo 教材 (動物行為學 2010) 93 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 Ayo 教材 (動物行為學 2010) 94 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 Ayo 教材 (動物行為學 2010) 95 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 Ayo 教材 (動物行為學 2010) 96 Complex relationships among genes, the nervous system, and behavior occur over different time scales. Ayo 教材 (動物行為學 2010) 97 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 Ayo 教材 (動物行為學 2010) 98 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 Ayo 教材 (動物行為學 2010) 99 問題與討論 [email protected] Ayo 台南 NUTN 站 http://myweb.nutn.edu.tw/~hycheng/ Ayo 教材 (動物行為學 2010) 100