Genes and Development

Transcription

1 Genes and Development

2 Two Main Questions The Classic Nature-Nurture Question: Are there biological reasons for why people are so different from one another? (Behavioral Genetics) The New Nature-Nurture Question: How is the nervous system built? (Developmental Neuroscience)

3 Two Main Questions The Classic Nature-Nurture Question: Are there biological reasons for why people are so different from one another? (Behavioral Genetics) NOT What matters more--the genes or the environment?

4 What makes a rectangle big? height or length? 6 9

5 What makes a rectangle big? Area = height X length! 6 9

6 What makes us X? nature or nurture? genes or environment?

7 Genetic and Environmental Forces Hereditary and environmental interactions are best illustrated by this model:

8 Genetic and Environmental Forces Hereditary and environmental interactions are best illustrated by this model:

9 Children get all of their genes from their parents. A gene is a segment of DNA that is the code for the production of one particular protein Genes affect development by specifying a protein template by regulating other genes

10 Children get all of their genes from their parents. Each parent contributes 50% of the child s genes

11 Because chromosomes come in pairs (one from each parent), so do genes Some pairs of genes are identical (homozygous) and some are not (heterozygous)

12 The difference between homozygous and heterozygous gene pairs (alleles) has implications for how the child s genotype affects his/her phenotype

13 2 GENOTYPE/Child PHENOTYPE/Child

14 2 GENOTYPE/Child PHENOTYPE/Child Two ways children s genes affect their behavior One gene can control behavior (Mendelian inheritance) Many genes can control behavior (Polygenic inheritance)

15 2 GENOTYPE/Child PHENOTYPE/Child A third of genes have two or more different forms, known as alleles. Some physical traits, such as straight hair, require matching recessive alleles, one from each parent, for expression. Others, such as curly hair, require only the inheritance of one dominant allele, which will override a recessive allele from the other parent. When traits are controlled by a single allele, a Mendelian distribution will be observed

16 Mendelian distribution: Mendel s Peas

17 Mendelian distribution: Hair Color

18 Mendelian distribution: Wizarding

19 Mendelian Psychological Traits Like the skin of peas, hair color, and wizarding, some psychological traits also appear to be controlled by a single gene Scott & Fuller (1965) found that all bansenjis were afraid of a novel person, whereas the cocker spaniels were seldom afraid. Was there a genetic link?

20 Mendelian Distribution: Fear Responses First, they crossbred pure cockers and pure basenjis. Some hybrids were raised by cockers; some by basenjis. All hybrids were fearful, like purebred basenjis They hypothesized that fearfulness was controlled by a singe dominant gene

21 Mendelian Distribution: Fear Responses To test their hypothesis, they crossbred the hybrids. They found the same pattern Mendel found with the peas. FF Ff

22 Mendelian Distribution: Fear Responses Finally, they backcrossed the original hybrids with purebred cockers. Half were afraid (like the basenji), and half were not (like the cockers), just as one would predict if a single fear-controlling gene were dominant.

23 Mendelian Distribution: PKU & SLI PKU Phenylketonuria: total language loss and mental retardation (prevented by monitoring the child s diet) SLI Specific Language Impairment has been linked to the FOXp2 gene

24 Polygenic Distribution Most traits and behaviors of psychological interest involve contributions by several genes, such as infant temperament shyness aggression risk-taking behavior empathy TV viewing

25 Polygenic Distribution When many individuals are tested for a polygenic characteristics, the results follow a normal distribution.

26 Population Genetics Population genetics attempts to find a role for genes by looking at differences between people and linking it to (genetic) family history ask how much variation in the behavior of a group is a function of genetic differences ( heritability, h 2 ) versus environmental differences If h2 = 1, all of the differences stem from genetic differences If h2 = 0, none of the differences stem from genetic differences If h2 =.5, half of the differences stem from genetic differences

27 Variation in Area World A World B Variation due to lengths Variation due to heights How much of the variation in area is a function of height versus width?

28 Variation in Behavior World A World B Variation due to lengths Variation due to heights How much of the variation in behavior is a function of genetic differences versus environmental differences?

29 Experiment to Establish Heritability

30 Tryon s Study of Maze Learning Tryon (1942) This chart depicts the progress Tryon made in selectively breeding rats for their ability to get through mazes after only a few errors. The critical step Tryon made was to cross-foster the rats (bright rats raised by dull rats, dull rats raised by bright ones). Regardless, offspring scores resembled those of their parents.

31 Estimating H 2 In humans, less control over environmental similarity is possible. Two common strategies: Compare identical twins raised apart (some environmental similarity) to identical twins raised together (more environmental similarity) to estimate environmentality the proportion of variance due to environmental variation Compare identical twins raised together (some environmental similarity) to fraternal twins raised together (same amount of environmental similarity?) to estimate heritability the proportion of variance due to genetic variation

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33 Family Studies of IQ Relationship Correlation MZ, reared together 0.86 DZ, reared together 0.60 MZ, reared apart 0.72 unrelated, reared together 0.00 h 2 = (MZ - DZ) x 2 = ( ) x 2 =.52 e 2 = (MZrt - MZra) = =.14

34 Three Laws of Behavioral Genetics Turkheimer (2000) First Law: All human behavioral traits are heritable. Second Law: The effect of being raised in the same family is smaller than the effect of genes. Third Law: A substantial portion of the variation in complex behavioral traits is not accounted for by the effects of genes or families.

35 Questions?

36 ENVIRONMENT/Child PHENOTYPE/Child 3

37 ENVIRONMENT/Child PHENOTYPE/Child 3 Genotypes are expressed differently in different environments. The norm of reaction is the range of all possible phenotypes in relation to all possible environments.

38 Family Studies of IQ Relationship Correlation MZ, reared together 0.86 DZ, reared together 0.60 MZ, reared apart 0.72 unrelated, reared together 0.00 H 2 IS NOT A CONSTANT! h 2 = (MZ - DZ) x 2 = ( ) x 2 =.52 e 2 = (MZrt - MZra) = =.14

39 Norm of reaction: Example #1 For the sake of argument, assume that depression/ happiness is entirely the result of genetics

40 Who is most likely to be depressed? A C Mr. A s identical twin has a history of depression Mr. C s fraternal twin has a history of depression B D Mr. B s identical twin has no history of depression Mr. D s fraternal twin has no history of depression

41 Norm of reaction: Example #1 A C D B Kendler et al. (1995) Am J Psychiatry, 152,

42 Norm of reaction: Example #1 Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene Avshalom Caspi, 1,2 Karen Sugden, 1 Terrie E. Moffitt, 1,2 * Alan Taylor, 1 Ian W. Craig, 1 HonaLee Harrington, 2 Joseph McClay, 1 Jonathan Mill, 1 Judy Martin, 3 Antony Braithwaite, 4 Richie Poulton 3 s = allele for short serotonin transporter l = allele for long serotonin transporter

43 Norm of reaction: Example #1 Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene Avshalom Caspi, 1,2 Karen Sugden, 1 Terrie E. Moffitt, 1,2 * Alan Taylor, 1 Ian W. Craig, 1 HonaLee Harrington, 2 Joseph McClay, 1 Jonathan Mill, 1 Judy Martin, 3 Antony Braithwaite, 4 Richie Poulton 3 s = allele for short serotonin transporter l = allele for long serotonin transporter

44 Norm of reaction: Example #1 Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene Avshalom Caspi, 1,2 Karen Sugden, 1 Terrie E. Moffitt, 1,2 * Alan Taylor, 1 Ian W. Craig, 1 HonaLee Harrington, 2 Joseph McClay, 1 Jonathan Mill, 1 Judy Martin, 3 Antony Braithwaite, 4 Richie Poulton 3 s = allele for short serotonin transporter l = allele for long serotonin transporter

45 Norm of reaction: Example #1 Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene Avshalom Caspi, 1,2 Karen Sugden, 1 Terrie E. Moffitt, 1,2 * Alan Taylor, 1 Ian W. Craig, 1 HonaLee Harrington, 2 Joseph McClay, 1 Jonathan Mill, 1 Judy Martin, 3 Antony Braithwaite, 4 Richie Poulton 3 s = allele for short serotonin transporter l = allele for long serotonin transporter

46 Norm of reaction: Example #1 Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene Avshalom Caspi, 1,2 Karen Sugden, 1 Terrie E. Moffitt, 1,2 * Alan Taylor, 1 Ian W. Craig, 1 HonaLee Harrington, 2 Joseph McClay, 1 Jonathan Mill, 1 Judy Martin, 3 Antony Braithwaite, 4 Richie Poulton 3 s = allele for short serotonin transporter l = allele for long serotonin transporter

47 Norm of Reaction Even when there is a substantial genetic contribution to a psychological trait, the amount of variation in the trait that is explained by genetic similarity (i.e., heritability) depends on the subjects environment

48 Norm of reaction: Example #2 Turkheimer et al. (2003) calculated IQ heritability for twins who differed in SES Sample median family income $22,000 (in 1997 dollars); 1997 US median $53,000

49 Norm of Reaction Does the norm of reaction imply that nature s role is somehow arbitrary, uncertain, or unreal? Consider PKU disorder In 100% of cases, the defective allele creates a defective enzyme that is from 0-50% effective as normal in breaking down phenylalanine In 100% of cases the build up of phenylalanine is poisonous to the brain and results in severe mental retardation Norm of reaction still applies: In an environment with NO phenylalanine, the defective gene won t make any difference in behavior In an environment WITH phenylalanine, the gene will make a huge difference in behavior

50 4. Child s Phenotype Child s Environment

51 4. Child s Phenotype Child s Environment Children are active sources of their own development in two ways: They actively evoke certain responses from others (e.g., calm, beautiful babies) They actively select surroundings and experiences conducive to their interests, talents, and personality characteristics. h2 + e 2 1

52 Questions?

53 Developmental Neuroscience So far we ve been talking about genes that vary from person to person, but what about the effects of genes shared by all people? Genes shared by all people do a lot of work recipe for bodies recipe for brains Developmental neuroscience is interested in the recipe (and cooking) of the nervous system

54 From blastocyst to brain Blastocyst Brain N.B. Not drawn to scale.

55 From blastocyst to brain All early mammalian cells have the same potential Only some get to be a brain How did they get to be so lucky?

56 From blastocyst to brain Six Basic Processes: 1. Gastrulation: cell specification into three distinct layers 2. Neurulation: specification of neural tissue 3. Neurogenesis: amplification of cell number 4. Neural Specialization: major brain divisions created by fate specification and differentiation 5. Synaptogenesis: formation of synapses 6. Synapse Elimination: refinement of circuits

57 1. Gastrulation neural ectoderm neural ectoderm mesoderm endoderm Before After

58 1. Gastrulation Blastocyst s three cell layers: endoderm: becomes the innermost layer of the embryo and produces the digestive tube and its associated organs (including the lungs) mesoderm: becomes sandwiched between the endoderm and ectoderm. generates the blood, heart, kidney, gonads, bones, and connective tissues. ectoderm: generates the outer layer of the embryo produces the surface layer (epidermis) of the skin and forms the nerves

59 2. Neurulation Neural tissue is formed from ectoderm cell layer How? Mesodermal cells secrete proteins (under control of the BMP4 gene) that induce some of the ectodermal cells to become neuroectoderm All cells in the adult nervous system come from these neuroectodermal cells

60 2. Neurulation neuroectoderm becomes the neural fold and later the plate the invagination in the neural plate becomes the neural tube (which eventually closes along the entire dorsal-ventral axis of the body)

61 3. Neurogenesis proliferation of neurons through cell division The number of neurons is determined by the Notch gene Due to TGF beta, neurogenesis does not occur evenly along the neural tube (which is sort of why the spinal cord is long and thin and the brain is big) the anterior nervous system is made first (they are the first neuroectoderm) then the posterior is made. the first cell that are made begin proliferating before the posterior is even form so first they have a head start second there are mitogenic factors in the anterior that continue proliferation in the brain that aren't present or not present as long in the spinal cord

62 4. Neural Specialization Embryonically, there are major subdivision of the brain These structures will functionally divide mature brain regions There is a large degree of sublevel differentiation in a mature brain

63 Neural Specialization in Embryogenesis Expression of Sonic Hedgehog is responsible for the mesencephalon/diencephalon boundary Expression of FGF8, which is secreted in a very precise region, is responsible for the midbrain/hindbrain boundary Expression of Hox genes define boundaries in the spinal cord

64 Neural Specialization in Embryogenesis Having a brain shaped bunch of neurons is not very useful The neurons have to communicate with each other That happens at synapses

65 5. Synaptogensis 1) target finding (via chemotaxis) 2) target signaling to create synapse 3) real synapse that secretes neurotransmitters

66 6. Synapse elimination Synapses don t make you smart At birth, too many neurons in what will become the auditory cortex are linked to the visual area

67 Words of caution 1. Observed changes in synaptic density do not support directed synaptogenesis Figure 4. Synaptic density in layer III, human middle frontal gyrus from birth to 8 years. Data from Huttenlocher (1979). Note the absence of data points between 1 and 5 years of age.

68 Words of caution Rakic et al. (1986, p. 234): if experience alters synaptic number during development it does so by causing selective survival of certain synapses, not by regulating their initial formation. Rakic et al. (1986) Concurrent Overproduction of Synapses in Diverse Regions of the Primate Cerebral Cortex

69 Words of caution Fig. 2. Mean synaptic density in synapses/100 µm 3 in auditory, calcarine, and prefrontal cortex at various ages. Open circles, visual cortex (area 17); filled circles, auditory cortex; x, prefrontal cortex (middle frontal gyrus). Huttenlocher & Dabholkhar (1998) Regional Differences in Synaptogenesis in Human Cerebral Cortex

70 Oh my god! Do I have to know ALL this for the exam???

71 Main Points 1. Development of the brain is the result of six processes What s the goal of each process? 2. Genes shared by everyone lay down the basic pattern of the brain.

72 Questions?

73 Is all of brain development a direct gene expression Or is some sort of experience required to build a brain?

74 What is the role of experience?

75 Why not make everything innate? Many adaptive abilities and preferences are innate Newborn colts can run moments after birth Newborn rats prefer sweet tasting foods to bitter ones Many adaptive abilities are not innate Speaking English Knowing how to drive

76 Why not make everything innate? Two theoretical limits on innateness Environmental change requires fast adaptation E.g., food preferences Genes are limited in number

77 Plasticity Capacity of brain to change in response to experience or damage Three kinds of evidence 1. Effects of general experiences that almost all normal infants have regardless of history, culture, child-rearing practices, etc. (experience-expectant plasticity) 2. Effects of specific, idiosyncratic experiences the child will have as a result of his or her own life circumstances (experience-dependent plasticity) 3. Recovery from brain damage

78 1. Experience-Expectant Plasticity Wiring of the brain partly results from general experiences patterned visual stimulation voices and other sounds movement manipulation These sources activate or stabilize some synapses and cause other synapses to be eliminated

79 1. Experience-Expectant Plasticity Experimental Evidence Experiments on cats and other mammals have shown that if a brain is chemically silenced during fetal development, the mammal ends up with significant abnormalities By shutting off auditory stimuli, Mriganka Sur rewired the brains of ferrets so that signals from their eyes fed into their auditory cortex Individual neurons in the auditory cortex responded to lines and stripes at a particular orientation and direction of movement Ferrrets could even move toward objects detectable by sight alone

80 1. Experience-Expectant Plasticity Evidence in humans Normally left hemisphere is used in processing language Develops here due to the brain s expectation of spoken language or innate organization?

81 1. Experience-Expectant Plasticity

82 1. Experience-Expectant Plasticity When a language depends on perception of spatial location and motion (as is the case for American Sign Language or ASL) areas within the right hemisphere are also part of the language systems of the brain Studies of visual processing in congenitally deaf individuals suggest that certain aspects of visual development are enhanced after auditory deprivation. These include the perception of and attention to peripheral visual space and to motion

83 2. Experience-Dependent Plasticity Brain is also wired by idiosyncratic experiences The brains of rats, cats, and monkeys raised in stimulus-rich environments differ from those raised in stimulus-poor environments More dendritic spines on cortical neurons More synapses per neuron Thicker cortex More supportive tissues (such as blood vessels and glial cells)

84 2. Experience-Dependent Plasticity Example from humans Violinists with years of practice have increased cortical representation of the fingers of the left hand Skilled Braille readers also have enlarged cortical representation of the hand they use to read Braille text

85 3. Recovery from Brain-Damage Recovery from brain damage shows that plasticity differs with age Very early damage (during neurogenesis and neuron migration) results in profound deficits Later damage (during synapse generation and elimination) is best because plasticity is highest But the best is not great--some problems only show up at later ages.

86 Synaptogenesis and Synapse Elimination

87 Limits on Plasticity Subcortical structures seem much less plastic hippocampus, which consolidates memories and supports mental maps amygdala, which colors experience with emotions hypothalamus, which is the source of the sex drive and other appetites