Neuroscience of Social Behavior - Week 6

More Key Points

1. A gene's influence on the average value of a trait (i.e.,whether it is inherited) differs from its influence on variability of that trait across individuals (its heritability). 2. Even in the realm of inherited traits—say, the inheritance of five fingers as the human average—you can't really say that there is genetic determination in the classically hard-assed sense of the word. This is because the inheritance of a gene's effect requires not just passing on the gene but also the context that regulates the gene in that manner. 3. Heritability scores are relevant ONLY to the environments in which the traits have been studied. The more environments you study a trait in, the lower the heritability is likely to be. Gene/environment interactions are ubiquitous and can be dramatic. Thus, you can't really say what a gene "does," only what it does in the environments in which it's been studied.

Estimating heritability

1. Family studies establish family resemblance, or familiarity 2. Adoption design as an experiment of nurture (no genetic relation to adopted parents) 3. Twin design as an experiment of nature (mono and di zygotic twins can see how genes contribute to traits)

KEY POINTS :)

1. Genes are not autonomous agents commanding biological events 2. Instead, genes are regulated by the environment, with "environment" consisting of everything from events inside the cell to the universe 3. Much of your DNA turns environmental influences into gene transcription, rather than coding for genes themselves; moreover, evolution is heavily about changing regulation of gene transcription, rather than genes themselves 4. Epigenetics can allow environmental effects to be lifelong, or even multigenerational 5. thanks to transposons, neurons contain a mosaic of different genomes 6. genes don't determine much

Criticisms of Twin and Adoption Studies

1. MZ and DZ don't really share environment equally - MZ twins are treated more similarly than DZ twins. 2. MZ twins experience life more similarly as fetuses (prenatal effects) 3. In adoption studies, the child is adopted soon after birth, but what about the prenatal environmental effects? (can influence behavior and fetal development) 4. Adoption studies assume parents and child don't share genes but many have similar racial or ethnic backgrounds (ancestry can increase chance of shared genes) 5. Range Restriction - Adoptive parents tend to be more educated, wealthier, and psychiatrically healthier than the typical biological parent - get effects where the environment is more homogenous (thus producing higher h2 when it is NOT in fact that high)

Family Studies - Disadvantages

A. Family History (pedigree) versus Family Study Methods - Difficulties and disadvantages: - Validity of diagnostic status in relatives - Results may depend on family size and structure - Hard to assess older generations as diagnoses may not mean the same thing or be as valid across age - Expensive and difficult to implement - Can't disentangle genes from environment don't know how everyone was living

Gene-Environment Interactions

"What are the effects of the gene on some behavior?" - "It depends on the environment" - Gene/Environment Interactions are VERY common (genes do DIFFERENT things in different environments) - makes sense, given that TFs are regulated by the environment - And some are quite powerful - A gene can do the opposite thing in two different environments. EX - 5HTT codes for a transporter that removes serotonin from the synapse - One variant of it increases the risk for depression ONLY if the person experienced childhood trauma - if you have the variant but NO trauma then you will not experience the 5HTT issue

Epigenetic Changes

"epigenetic" changes were relevant to events, particularly in childhood, causing persistent effects on the brain and behavior - EX - pair-bonding prairie voles; when females and males first mate, there are epigenetic changes in regulation of oxytocin and vasopressin receptor genes in the nucleus accumbens, that target of mesolimbic dopamine projection - CHANGES: environmental input results in a chemical being attached tightly to a promoter, or to some nearby structural proteins surrounding DNA. The result of either is that TFs can no longer access or properly bind to the promoter, thus silencing the gene - can be multigenerational changes and can be passed on by both egg and sperm - epigenetically mediated mechanisms of inheritance are REAL - not only does environment regulate genes, but it can do so with effects that last days to lifetimes

Gene Transcription

- First Step - Process by which a DNA sequence is copied to produce a complementary mRNA strand - the transfer of genetic information from DNA into RNA - Like replication, but making RNA from DNA - Beginning of the process that ultimately leads to the translation of the genetic code (via mRNA) into a protein - replaces Thymine with Uracil

Gene Translation

- Second Step - Ribosomes (contain ribosomalRNA - rRNA) make proteins from the messages encoded in mRNA - genetic instructions for a polypeptide chain are 'written' in the DNA as a series of 3- nucleotide 'words.' - Codon on mRNA - Anti-codon on tRNA which is BOUND to an amino acid sequence that matches the sequence on the codon mRNA - once bound the anti-codon links the polypeptide to the growing chain and then leaves empty - occurs in the ribosomes - 'U' (uracil) replaces 'T' in RNA - which is the genetic code.

Genes influence biological systems

Genes affect biological systems which lead to characteristics (traits) in a person which influence a trait or behavior we are examining (watching TV)

MAIN Sapolsky points

Genes are NOT autonomous agents commanding biological events - don't determine much - Genes CANNOT override the environment - Genes are regulated by the environment, which includes everything that happens inside the cell to the universe - Much of your DNA turns environmental influences into gene transcription, rather than coding for genes themselves - evolution is heavily changing gene transcription, rather than the genes themselves - Epigenetics can allow environmental effects to be lifelong, or even multi-generational

The role of genes in behavior

Genes are relevant to everything - Many NTs and hormones are coded for by genes as well as molecules that construct or degrade those messengers, as are their receptosr - so are GFs guiding brain plasticity - Genes typically come in different versions; we each consist of an individuated orchestration of the different versions of our approximately twenty thousand genes. Carries two burdens 1. reflects many people being troubled by linking genes with behavior - monstrous distortions of genetics have fueled those who lynch, ethnically cleanse, or march children into gas chambers 2. people who are overly enthusiastic about the subject - Overenthusiasm for genes can reflect a sense that people possess an immutable, distinctive essence - study concerning "moral spillover" based on kinship - found people see essentialism embedded in bloodlines—i.e., genes (pay for the crimes of your grandfather that he never answered for) - genes are important but they're far less so than often thought

Heritability of various aspects of cognitive development

Heritability of various aspects of cognitive development is very high - around 70 percent for IQ) in kids from high-socioeconomic status (SES) families but is only around 10 percent in low-SES kids - higher SES allows the full range of genetic influences on cognition to flourish, whereas lower-SES settings restrict them - genes are nearly irrelevant to cognitive development if you're growing up in awful poverty— poverty's adverse effects trump the genetics - heritability of alcohol use is lower among religious than nonreligious subjects—i.e., your genes don't matter much if you're in a religious environment that condemns drinking - ENVIRONMENT is EXTREMELY powerful

Heritability (h2)

In a population, if genes strongly influence the variability of the trait around the average level, it has high heritability - variance AROUND a mean - EX - In a population of 1000 clones who all have the same genetics, if there's any variation in their phenotype (some are more polite), then it would be due 100% to environment, and h2 = 0% (NOT genetic at all) - In a population of 1000 people with exactly the same environment, if there's any variation (some are more aggressive), then it would be no effect of environment and h2 = 100% (FULLY genetic) • KEY - To really understand the heritability of some behavior, it has to be looked at across many different environments (this increases heritability and shows that variation is NOT due to environment despite the high difference in environment)

Law of Dominance - 3rd Law

In many traits one allele is dominant over the other allele. The "weaker (recessive" allele is only expressed when it is paired with another recessive allele - One of the factors for a pair of inherited traits will be dominant and the other recessive, unless both factors are recessive - Dominant homozygous - TT - Dominant hetrozygous - Tt - Recessive homozygous - tt

Sex-Determining Region of Y Chromosome (SRY)

Location of SRY gene on Y chromosome - SRY encodes testis-determining factor (TDF) - Causes development of testes and testicular hormones (androgens) - Makes fetus develop as male where the default pathway is female - causes the development of the Wolffian duct and the reduction of the Mullirian duct

Law of Segregation - 1st Law

Mendel's law that states that the pairs of homologous chromosomes separate in meiosis so that only one chromosome from each pair is present in each gamete - only get ONE from each parent - Each trait is controlled by two factors which separate or segregate into gametes - genetic material from EACH parent - get one from mom and one from dad but each parent has two copies (TT, Tt, tt) - get Dominant and recessive phenotypes. (1) Parental generation (2) F1 generation (3) F2 generation.

DNA Replication

Copying of a double-stranded DNA molecule - Each DNA strand holds the same genetic information, so each strand can serve as a template for the new, opposite strand - The parent (template) strand is preserved and the daughter (new) strand is assembled from nucleotides and creates NEW DNA - Resulting double-stranded DNA molecules are identical - thus you get 2 identical DNA molecules - DNA copies due to cell division - this is especially important in fetal development as cells double DNA needs to as well - occurs prior to cell division - Replication occurs prior to cell division, because the new, daughter cell will also need a complete copy of cellular DNA

Gregor Menel & Mendelian Inheritance

Czech monk and scientist - worked with pea plants, making numerous crosses with varieties of pure breeding pea plants (varieties that bred true for a characteristic each generation). - Presented his paper, "Experiments on Plant Hybridization," at two meetings of the Natural History Society of Brno in Moravia on 8 February and 8 March 1865 - Had little impact, and was only cited about three times over the next thirty-five years

Genes

DNA segments that serve as the key functional units in hereditary transmission - have specific places on chromosomes

The Central Dogma of Gene Expression

DNA, transcription, mRNA, translation, protein - goal - a cell need a structural and functional change to occur --> has to go to DNA and find out what to do (increase cellular glucose) --> cell reads DNA and copies it using proteins --> makes NEW proteins in ribosomes to enact the desired cellular function

TF Complications

Different transcription profiles result in different TFs being needed (2-3 genes can be needed to create one protein) - two different genes would have two different TFs - But to be transcribed together a THIRD TF is needed to activate both - Gets more complicated with more and more genes needed - each TF is coded by a gene itself - thus much of the genome is genes for TFs (regulatory effect) - The more genomically complex the organism, the larger the percentage of the genome devoted to gene regulation by the environment - EVOLUTION tends to work on gene regulation (TFs) and not genes themselves

DNA Structure

Double stranded molecule - two deoxyribose-phosphate chains - base pairs, linked by hydrogen bonds Purine Bases (double ring) Adenine & Guanine Pyrimidine Bases (single ring)Cytosine & Thymine - A-T pair - C-G pair

Exon

a segment of a DNA or RNA molecule containing information coding for a protein or peptide sequence - coding region - present in mRNA

The Dopamine System - COMT

after dopamine binds to receptors, it floats off and must be removed from the synapse - One route involves its being degraded by the enzyme catechol-O- methyltransferase (COMT) - Among the variants of the COMT gene is one associated with a more efficient enzyme. "More efficient" = better at degrading dopamine = less dopamine in the synapse = less dopamine signaling - The highly efficient COMT variant is associated with higher rates of extroversion, aggression, criminality, and conduct disorder - Moreover, in a gene/environment interaction straight out of the MAO-A playbook, that COMT variant is associated with anger traits, but only when coupled with childhood sexual abuse - Intriguingly, the variants seem pertinent to frontal regulation of behavior and cognition, especially during stress - In addition to degradation, NTs can be removed from the synapse by being taken back up into the axon terminal for recycling - Dopamine re-uptake is accomplished by the dopamine transporter (DAT) - he DAT gene comes in different variants, and those that produce higher levels of synaptic dopamine (transporter variants that are less efficient) in the striatum are associated with people who are more oriented toward social signaling—they're drawn more than average to happy faces, are more repelled by angry faces, and have more positive parenting styles - How these findings merge with the findings from the DRD4 and COMT studies (i.e., fitting risk taking with a preference for happy faces) is not immediately apparent - these findings are not consistent, no doubt reflecting unrecognized gene/environment interactions - COMT literature is majorly messy, for the inconvenient reason that the enzyme also degrades norepinephrine. - These effects are tiny. For example, knowing which DRD4 variant someone has explains only 3 to 4 percent of the variation in novelty-seeking behavior

Genes Related to Steroid Hormones

testosterone - not a protein, meaning there isn't a testosterone gene - However, there are genes for the enzymes that construct testosterone, for the enzyme that converts it to estrogen, and for the testosterone (androgen) receptor - most work has focused on the gene for the receptor, which comes in variants that differ in their responsiveness to testosterone - a few studies have shown that among criminals, having the more potent variant is associated with violent crimes - A related finding concerns sex differences in structure of the cortex, and adolescent boys with the more potent variant show more dramatic "masculinization" of the cortex. An interaction between receptor variant and testosterone levels occurs. High basal testosterone levels do not predict elevated levels of aggressive mood or of amygdaloid reactivity to threatening faces in males—except in those with that variant - Similar themes concern the genetics of the estrogen receptor - different receptor variants are associated with higher rates of anxiety among women, but not men, and higher rates of antisocial behavior and conduct disorder in men, but not women - in genetically manipulated mice, the presence or absence of the receptor gene influences aggression in females . . . depending on how many brothers there were in the litter in utero— gene/environment again. Once again, the magnitude of these genetic influences is tiny. - genes related to glucocorticoids, particularly regarding gene/environment interactions - For example, there is an interaction between one variant of the gene for a type of receptor for glucocorticoids (for mavens: it's the MR receptor) and childhood abuse in producing an amygdala that is hyperreactive to threat - Then there is a protein called FKBP5, which modifies the activity of another type of receptor for glucocorticoids (the GR receptor); one FKBP5 variant is associated with aggression, hostility, PTSD, and hyperreactivity of the amygdala to threat—but only when coupled with childhood abuse - Buoyed by these findings, some researchers have examined two candidate genes simultaneously. For example, having both "risk" variants of 5HTT and DRD4 synergistically increases the risk of disruptive behavior in kids—an effect exacerbated by low socioeconomic status ISSUES: 1. results aren't terribly consistent from one study to the next 2. effect sizes are small. Knowing what variant of a candidate gene someone has (or even what variants of a collection of genes) doesn't help much in predicting their behavior. 3. A major reason is that, after getting a handle on 5HTT and DRD4 interactions, there are still roughly 19,998 more human genes and a gazillion more environments to study

Genotype

the alleles or variants the organism carries in a particular gene or set of genes - contribute to phenotypes—but could vary in how much

Genome

the complete instructions for making an organism, consisting of all the genetic material in that organism's chromosomes - the COMPLETE complement of an organism's DNA

Alternative Splicing

can generate multiple unique proteins from a single stretch of DNA; so much for "one gene specifies one protein"—this gene specifies seven - If you have 3 exons and 2 introns you could have multiple combos as different enzymes remove different exons along with the introns - 90 percent of human genes with exons are alternatively spliced - when a gene is regulated by multiple TFs, each can direct the transcription of a different combination of exons - splicing enzymes are proteins, meaning that each is coded for by a gene

Law of Independent Assortment - 2nd Law

the law that states that genes separate independently of one another in meiosis - independently provided by mother and father - different characters or traits were inherited separately - Traits did not interact during inheritance and are inherited separately or independently of one another - Analogous to flipping two quarters, the outcome of the toss of the first quarter (resulting in a heads or tails) will not influence the outcome in a toss of the second quarter.

Pedigree Diagram

the method of diagramming inheritance that shows the phenotypes of individuals from multiple generations in a family - A diagram that shows the occurrence of inherited traits across two or more generations of a family - Carrier is half filled - affected trait is fully colored - unaffected is not colored - say nothing about genes, chromosomes, alleles, etc.

Phenotype

the set of observable characteristics or traits of an organism - hair color, walking style, certain allergies - affected by genotypes & environment - traits that you can SEE or OBSERVE

Epigenetics

the study of environmental influences on gene expression that occur without a DNA change - Changes in the heritable phenotype that do not involve alterations to the DNA sequence - Many Epigenetic Mechanisms ( development in utero or childhood, environmental chemicals, drugs, aging and diet) - an event happens to cause TFs to no longer bind to the promoter --> transcription no longer happens --> the gene is SILENCED --> no protein - Can happen for short periods, lifelong, and even multi- generations (can get phenotypic changes that persist for generations and are inherited)

Chromosomes

threadlike structures made of DNA molecules that contain the genes - DNA is organized into chromosomes

Mendel's Crosses

used upper case letters to stand for alleles that were expressed whenever they were in the genotype, i.e., dominant alleles, and lower case letters to stand for alleles expressed only in the absence of the dominant, i.e., recessive alleles - True breeding tall pea plants carried the factors TT whereas short pea plants carried the factors tt - F1 generation - the resulting plants were all tall and carried the genotype Tt - F2 generation, 3⁄4 of the plants were tall, and 1⁄4 were short. The genotypes in the F2 generation were 1⁄4 TT, 1⁄2 Tt and 1⁄4 tt

Thomas Bouchard Twin study

found a pair of identical twins who were—get this—separated at birth and adopted into different homes, with no knowledge of each other's existence until being reunited as adults - same genes, different environments thus, similarities in behavior probably reflect genetic influences - One twin pair who lived VERY different lives were reunited and studied by Bouchard, they warily got to know each other, discovering numerous shared behavioral and personality traits including . . . flushing the toilet before use

Complexity among TFs

genes can be regulated by multiple TFs - each TF usually activates more than one gene, meaning that multiple genes are typically activated in networks - EX - cell injury causes a TF called NF-κB to activate a network of inflammation genes - the human genome codes for about 1,500 different TFs, contains 4,000,000 TF-binding sites, and the average cell uses about 200,000 such sites to generate its distinctive gene-expression profile

Genes and Behavior

genes have a lot to do with behavior - all behavioral traits are affected to some degree by genetic variability - But their effects are supremely context dependent. Ask not what a gene does. Ask what it does in a particular environment and when expressed in a particular network of other genes - genes aren't about inevitability. Instead they're about context-dependent tendencies, propensities, potentials, and vulnerabilities

Limited power of genes

genes specify protein structure, shape, and function--> proteins do virtually everything, but genes don't "decide" when a new protein is made

Family Resemblance for Complex Traits

idea formed the roots of behavioral genetics - What traits - physical or psychological - run in families? - Why do these traits run in families? What is the aetiology of such traits? aetiology - do smaller bits of traits get passed on and combine with OTHER parts of the phenotype that is involved in creating a certain trait? - How do genes and environments cause such traits? - How can we estimate these genetic and environmental influences? - How can we study the role of genes and the environment? - must use HEAVY statistics and quantification

The Serotonin System

low levels of serotonin fostering impulsive antisocial behavior - There are lower-than-average levels of serotonin breakdown products in the bloodstreams of people with that profile, and of serotonin itself in the frontal cortex of such animals - Even more convincingly, drugs that decrease "serotonergic tone" (i.e., decreasing serotonin levels or sensitivity to serotonin) increase impulsive aggression; raising the tone does the opposite. - PREDICTIONS - should be associated with impulsive aggression, as they will produce low serotonin signaling: Low-activity variants of the gene for tryptophan hydroxylase (TH), which makes serotonin High-activity variants of the gene for monoamine oxidase-A (MAO-A), which degrades serotonin High-activity variants of the gene for the serotonin transporter (5HTT), which removes serotonin from the synapse Variants of genes for serotonin receptors that are less sensitive to serotonin - ALL WRONG LOL - shows that for each of those genes the results are inconsistent and generally go in the opposite direction from "low serotonin = aggression" 5HTT, the serotonin transporter gene, is consistently in the opposite direction from what's expected - Two variants exist, with one producing less transporter protein, meaning less serotonin removed from the synapse - This variant, producing more serotonin in the synapse, is associated with more impulsive aggression, not less. Thus, according to these findings, "high serotonin = aggression"

Modular Construction of Genes

most genes are not coded for by a continuous stretch of DNA. Instead there might be a stretch of noncoding DNA in the middle - Exons and Introns - Many genes are broken into numerous exons (with, logically, one less intron than the number of exons) - The RNA photocopy of the gene initially contains the exons and introns; an enzyme removes the intronic parts and splices together the exons - Introns and exons destroy this simplicity of a gene coding for a CERTAIN protein by alternative splicing

TFs and Gene Activation

multiple types of TFs in a cell, each binding to a particular DNA sequence constituting a particular promoter EXAMPLE: - Take a genome consisting of genes A and B, meaning three different transcription profiles—A is transcribed, B is transcribed, A and B are transcribed —requiring three different TFs - three genes with seven transcription profiles thus you need 7 TFs - As the number of genes in a genome increases, the number of possible expression profiles increases exponentially - As does the number of TFs needed to produce those profiles - TFs are usually proteins, coded for by genes - there must exist three more genes, each coding for one of those TF - requires TFs that activate those genes & TFs for the genes coding for those TFs - infinite loop of TFs is stopped by TFs regulate one another's transcription - **the longer the genome the greater the percentage of genes coding for TFs** - ****the more genomically complex the organism, the larger the percentage of the genome devoted to gene regulation by the environment**** - evolution of genes is less important than the evolution of regulatory sequences upstream of genes

Candidate Genes

requires a list of plausible suspects—genes already known to be related to some behavior - if you're interested in a behavior that involves serotonin, obvious candidate genes would include those coding for enzymes that make or degrade serotonin, pumps that remove it from the synapse, or serotonin receptors - Pick one that interests you, and study it in animals using molecular tools to generate "knockout" mice or "transgenic" mice - Make manipulations like these only in certain brain regions or at certain times - examine what's different about behavior

Adoption Studies

Purpose - an experiment of nurture, provide the most direct estimates of shared environmental influences - Also can provide estimates of genetic influences, or heritability - Design in which genetic and environmental contributions to a trait or disease are cleaved - an "experiment of nurture, as well as nature" - Can draw inferences regarding genetic influences from: 1. Correlation between biological parents and adoptees 2. Difference in correlation (r) between adoptive parents and their biologically-related vs. adopted children 3. Difference in correlation between biologically-related and adoptive siblings. - MAIN QUESTION - these are HIGHLY quantitive and we can study the genetic v. environmental influences on traits and behavior - Can draw inferences regarding shared environmental influences from: 1. Correlation between adoptive parents and adoptees 2. Correlation between adoptive siblings 3. Difference in correlation between adoptees and their adoptive parents versus their biological parents - One may get different estimates of genetic and environmental influences from parent-offspring versus sibling correlations

Family Studies

Purpose: - Family studies establish family resemblance for a trait or disorder (familiarity) ---how much does a trait travel through families - Shows family resemblance for 2 or more traits or disorders (co-familiarity) - Simple concept - Family members show greater resemblance for a disorder or trait than do unrelated individuals - Simplest Design - Contrast rates of a disorder in the relatives of affected individuals with rates in unaffected controls - Complex design - Contrast rates of a disorder in the relatives of affected individuals with rates in the relatives of individuals affected with a DIFFERENT disorder - typically the more distant from an affected relative you are in a blood line the LESS likely you are to be affected by that trait but it still can happen (schizophrenia example) - can study COMPLEX traits - Although each individual gene follows Mendelian laws of inheritance - traits are influenced by many genes, which result in the traits being quantitative

Tesser Quantitive Study

Tesser, a social psychologist, used data from Nick Martin's twin studies (3,000 pairs) in Australia to examine the heritability of attitudes (opinion about various things) - Found the higher the heritability of that attitude, the more resistant to change the attitude was in an American college sample - knowing heritability allowed Tesser to present attitudes to UG students - found that the more heritability attributed to the attitude from Martin's data the harder it was to change that attitude in the lab - tested a bunch of different heritable attitudes - showed that genes don't determine attitude but influences the biological systems that influence traits

Francis Galton

1822-1911 random accomplishments: - Over 340 papers and books - Developed regression and correlation methods - Introduced methods of questionnaires and surveys - Devised a method of fingerprinting for forensics - Developed use of maps for meteorology - Invented the silent dog whistle - Meteorology in his 40s - In 1859 his cousin Charles Darwin publishes Origin of Species - became preoccupied with individual differences and inheritance of abilities (genetics research) - Galton developed behavioral genetics - Coined "nature versus nurture" in English Men of Science: Their Nature and Nurture (1874) • Developed the twin method in 1875 • Coined "eugenics" in Inquiries in Human Faculty and its Development in 1883 (BAD)

Human Genome

23 chromosome pairs - Fully sequenced in 2001 - 19,000-20,000 protein- coding genes - coding region only 1.5-5% of the genome and causes transcription and translation of proteins to affect cellular function - The rest are non- coding RNA genes, regulatory DNA sequences, introns - non-coding regions make TFs

Behavioral Genetics

Began with family studies - if everyone in a family does it, it must be genetic. This was confounded by environment running in families as well - next approach depended on closer relatives having more genes in common than distant ones. Thus, if a trait runs in a family and is more common among closer relatives, it's genetic. But obviously, closer relatives share more environment as well—think of a child and parent versus a child and grandparent - third approach - Consider someone's biological aunt (i.e., the sister of a parent), and the uncle who married the aunt. The uncle shares some degree of environment with the individual, while the aunt shares the same, plus genes. Therefore, the extent to which the aunt is more similar to the individual than the uncle reflects the genetic influence. But as we'll see, this approach has problems. More sophistication was needed

Behavior Genetics and Molecular Genetics

Behavior genetics has gotten a huge boost by incorporating molecular approaches - caveats: - (a) not all of these findings consistently replicate - (b) effect sizes are typically small (in other words, some gene may be involved, but not in a major way) - (c) the most interesting findings show gene/environment interactions

Heritability Estimates

Behavior genetics studies usually produce a number called a heritability score - What's a heritability score? "What does a gene do?" is at least two questions - How does a gene influence average levels of a trait? - How does a gene influence variation among people in levels of that trait? Inherited trait - If genes strongly influence average levels of a trait, that trait is strongly inherited Heritability - If genes strongly influence the extent of variability around that average level, that trait has high heritability - it is a population measure, where a heritability score indicates the percentage of total variation attributable to genetics - difference between an inherited trait and heritability generates at least two problems that inflate the putative influence of genes 1. People confuse them - often mistakenly believe that if a trait is strongly inherited, it's thus highly heritable 2. research consistently inflates heritability measures, leading people to conclude that genes influence individual differences more than they do

Karl Pearson (1857-1936)

British mathematician and biostatistician - founded the world's first statistic department at UCL (London) in 1911 - Protégé of Galton - Developed the correlation coefficient r, chi-square, the p-value, and perhaps even the first histogram - also a EUGENICIST - along with Galton they were both promoters of eugenics - the aim to improve the genetic quality of the human population - Wrote essays warning of the dangers of "inferior races" and how civilization could be improved if feeble people weren't allowed to have offspring (used by the Nazis in WW2) - SO popular in his time that he was offered an OBE and Knighthood— both he turned down because he considered himself a socialist and freethinker (people genuinely thought they could improve society by thinking this way)

Example of gene/environment interaction

EXAMPLE 1: disease phenylketonuria arises from a single gene mutation; skipping over details, the mutation disables an enzyme that converts a potentially neurotoxic dietary constituent, phenylalanine, into something safe - if you eat a normal diet, phenylalanine accumulates, damaging the brain -eat a phenylalanine-free diet from birth, and there is no damage - What are the effects of this mutation on brain development? It depends on your diet. What's the effect of diet on brain development? - It depends on whether you have this (rare) mutation EXAMPLE 2: depression, a disease involving serotonin abnormalities - A gene called 5HTT codes for a transporter that removes serotonin from the synapse; having a particular 5HTT variant increases the risk of depression . . . but only when coupled with childhood trauma - What's the effect of 5HTT variant on depression risk? It depends on childhood trauma exposure - What's the effect of childhood trauma exposure on depression risk? It depends on 5HTT variant (plus loads of other genes, but you get the point) EXAMPLE 3: concerns FADS2, a gene involved in fat metabolism - One variant is associated with higher IQ, but only in breast-fed children. Same pair of "what's the effect" questions, same "it depends" answers EXAMPLE 4: studied mouse strains known to have genetic variants relevant to particular behaviors - ensured that the mice from a particular strain were essentially genetically identical in all three labs - standardized everything (literally ALL lab procedures, times, EVERYTHING) - RESULTS - Some gene variants showed massive gene/environment interactions, with variants having radically different effects in different labs - Even minimal differences in the environment affected the gene/environment interactions -!! most of the gene variants were so sensitive to environment that gene/environment interactions occurred even in obsessively similar lab settings, where incredibly subtle (and still unidentified) environmental differences made huge differences in what the gene did !! - **it's not meaningful to ask what a gene does, just what it does in a particular environment**

GWAS (genome wide association study)

Examine, say, the gene for hemoglobin and look at the eleventh nucleotide in the sequence; everyone will pretty much have the same DNA letter in that spot - BUT there are little hot spots of variability, single nucleotides where, say, two different DNA letters occur, each in about 50 percent of the population (and where this typically doesn't change the amino acid being specified, because of DNA redundancy) - there are more than a million of such "SNPs" (single-nucleotide polymorphisms) scattered throughout the genome—in stretches of DNA coding for genes, for promoters, for mysterious DNA junk - Collect DNA from a huge number of people, and examine whether particular SNPs associate with particular traits - If an SNP that's implicated occurs in a gene, you've just gotten a hint that the gene may be involved in that trait - A GWAS study might implicate scads of genes as being associated with a trait and hopefully, some will be candidate genes already known to be related to the trait - But other identified genes may be mysterious. Now go check out what they do ANOTHER APPROACH - - take two populations, one with and one without a degenerative muscle disease - Take a muscle biopsy from everyone, and see which of the ~20,000 genes are transcriptionally active in the muscle cells - With this "microarray" or "gene chip" approach, you look for genes that are transcriptionally active only in diseased or in healthy muscle, not in both. Identify them, and you have some new candidate genes to explore Studies show there are hundreds of genetic variants were implicated in regulating height - A handful of genes identified were known to be involved in skeletal growth, but the rest was terra incognita - The single genetic variant identified that most powerfully predicted height explained all of 0.4 percent—four tenths of one percent—of the variation in height, and all those hundreds of variants put together explained only about 10 percent of the variation - the single most explanatory genetic variant identified accounted for only 0.3 percent of the variation in BMI - both height and BMI are highly "polygenic" traits. Same for age of menarche - Moreover, additional genes are being missed because their variants are too rare to be picked up by current GWAS techniques. Thus these traits are probably influenced by hundreds of genes - 2013 GWAS study examined the genetic variants associated with educational attainment - most predictive genetic variant accounted for 0.02 percent—two hundredths of one percent—of the variation - All the identified variants together accounted for about 2 percent of the variation - review of candidate genes barely scratches even the surface of the surface - candidate gene approaches show that the effect of a single gene on a behavior is typically tiny - GWAS show that these behaviors are influenced by huge numbers of genes, each one playing only a tiny role - translates into non-specificity - serotonin transporter gene variants have been linked to risk of depression, but also anxiety, obsessive-compulsive disorder, schizophrenia, bipolar disorder, Tourette's syndrome, and borderline personality disorder. In other words, that gene is part of a network of hundreds of genes pertinent to depression, but also part of another equally large and partially overlapping network relevant to anxiety, another relevant to OCD

Difference Between a Trait Being Inherited and Having a High Degree of Heritability

Example - a trait that is highly inherited but has low heritability - What do genes have to do with humans averaging five fingers per hand? TONS - it's an inherited trait - What do genes have to do with variation around that average? NOT MUCH - cases of other than five fingers on a hand are mostly due to accidents - While average finger number is an inherited trait, the heritability of finger number is low—genes don't explain individual differences much Example - a trait that is not highly inherited but which has high heritability - What do genes directly have to do with humans being more likely than chimps to wear earrings? NOT MUCH - Individual differences among humans—how much do genes help predict which individuals are wearing earrings at a high school dance in 1958? TONS - you had two X chromosomes, you probably wore earrings, but if you had a Y chromosome, you wouldn't have been caught dead doing so - Thus, while genes had little to do with the prevalence of earrings among Americans in 1958 being around 50 percent, they had lots to do with determining which Americans wore them - Thus, in that time and place, wearing earrings, while not a strongly inherited trait, had high heritability.

Darwin's Theory of Natural Selection

How do new species emerge? - Three essential elements for natural selection to operate: 1. Variation in the expression of a trait among members of a species (height, behavior, beak size) 2. Variation must be heritable (genetically transmitted) 3. A struggle for existence among members of a species, idea promoted by Malthus, an economist / political scientist (survival of the fittest due to limited resources) - Result: individuals will have differential reproductive success and gradual changes will occur in a population - gradual changes will shift the characteristics of populations and new species will form from an ancestral species

Zietsch Study

Human same-sex sexual behaviour (SSB) is heritable, confers no immediately obvious direct reproductive or survival benefit and can divert mating effort from reproductive opportunities - presents a Darwinian paradox: why has SSB been maintained despite apparent selection against it? - They showed that genetic effects associated with SSB may, in individuals who only engage in opposite-sex sexual behavior (OSB individuals), confer a mating advantage - Show that, among OSB individuals, genetic effects associated with SSB are associated with having more opposite-sex sexual partners - Computer simulations suggest that such a mating advantage for alleles associated with SSB could help explain how it has been evolutionarily maintained - Caveats - include the cultural specificity of UK and US samples - the societal regulation of sexual behaviour in these populations - the difficulty of measuring mating success - the fact that measured variants capture a minority of the total genetic variation in the traits - homosexual behavior is heritable - if you have SSB traits but are OSB you may be more likely to have MORE sexual partners which increases your likelihood to reproduce - Used data from: - UK Biobank, in which 500,000 people born between 1934 and 1971 were recruited in the UK in 2006 and 2010 - provided DNA samples and completed extensive questionnaire data, including questions related to sexual behavior - US (23andMe and AddHealth) - DNA and questionnaire data - added another 5000 people to the data set RESULTS: - showed that OSB/SSB is genetically based but is a VERY large proportion of the genome that has influence - SNP heritability NOT driven by a small number of genes of large effect but rather a VERY large number of genes that is very spread out across the genome - correlated traits were openness to experience, risk-taking behavior and others

Inherited trait

If genes strongly influence average levels of a trait, that trait is strongly inherited (like height or eye color) - gives the MEAN - compare with another species or population

Gene/Environment Interactions

Imagine a growth pattern in environment A of 1, 1, and 1 for the three gene variants, while in environment B it's 10, 10, and 10 - considering the combined data from both environments, heritability is zero— variation is entirely explained by which environment the plant grew in - Instead, in environment A it's 1, 2, and 3, while in environment B it's also 1, 2, and 3 - Heritability is 100 percent, with all variability in height explained by genetic variation - say environment A is 1, 2, and 3, and environment B is 1.5, 2.5, 3.5 - Heritability is somewhere between 0 percent and 100 percent - HOWEVER, Environment A: 1, 2, 3. Environment B: 3, 2, 1 - In this case even talking about a heritability score is problematic, because different gene variants have diametrically opposite effects in different environments - a gene/environment interaction, where qualitative, rather than just quantitative, effects of a gene differ by environment -***"What are the effects of the gene on some behavior?" - "It depends on the environment." - "What are the effects of environment on this behavior?" - "It depends on the version of the gene." "It depends" = a gene/environment interaction

The Dopamine System - DRD4

Lots of work has examined the genes involved, most broadly showing that variants that produce lowered dopamine signaling (less dopamine in the synapse, fewer dopamine receptors, or lower responsiveness of these receptors) are associated with sensation seeking, risk taking, attentional problems, and extroversion - Such individuals have to seek experiences of greater intensity to compensate for the blunted dopamine signaling - research has focused on one particular dopamine receptor; there are at least five kinds (found in different parts of the brain, binding dopamine with differing strengths and duration), each coded for by a gene - Work has focused on the gene for the D4 dopamine receptor (the gene is called DRD4), which mostly occurs in the neurons in the cortex and nucleus accumbens - One stretch of the gene is repeated a variable number of times, and the version with seven repeats (the "7R" form) produces a receptor protein that is sparse in the cortex and relatively unresponsive to dopamine - This is the variant associated with a host of related traits—sensation and novelty seeking, extroversion, alcoholism, promiscuity, less sensitive parenting, financial risk taking, impulsivity, and, probably most consistently, ADHD - kids with the 7R variant are less generous than average. But only if they show insecure attachment to their parents. Secure- attachment 7Rs show more generosity than average. Thus 7R has something to do with generosity—but its effect is entirely context dependent - In another study 7R students expressed the least interest in organizations advocating prosocial causes, unless they were given a religious prime,* in which case they were the most prosocial. One more—7Rs are worse at gratification-postponement tasks, but only if they grew up poor - don't ask what a gene does; ask what it does in a particular context

DNA --> Protein

MAKING DNA Making a copy of the genetic material = Replication - duplication MAKING RNA - Transferring genetic code (DNA) to RNA = Transcription MAKING PROTEINS Making proteins = Translation - The translation of biology translates DNA information into proteins

Combining Molecular and Behavioural Genetics

Major Methods for Behavioral Genetics Traditional Behavioral Genetics - Twin, Adoption, and Family Studies Contemporary Behavioral Genetics - focuses more on Genomics - typically require very large sample sizes Candidate Genes - genes thought to cause specific phenotypes - do people with this allele show the desired phenotype? - very hard to replicate as phenotypes are determined by a LARGE number of genes and interactions Genome-wide association studies (GWAS) - relationship of MILLIONS of polymorphisms that could occur from allele combos, see how they might be associated with certain phenotypes - NOT theoretically determined - point and pray vibes SNP (Single Nucleotide Polymorphisms) heritability - more than 1 million SNPs in human genome - look for small differences and variations at points in the genome - you can see if these variations show a relationship between a phenotype of interest

Replication Mistakes & Mutations

Mutation is a change in the nucleotide base sequence of a genome - is RARE - Problem - Wrong amino acid may result in a non- functional protein due to improper folding - USUALLY bad news but sometimes leads to a protein having a novel property that improves ability of organism and its descendants to survive and reproduce (leads to a positive evolutionary trait)

Neuropeptides Oxytocin and Vasopressin

Oxytocin and vasopressin are involved in prosociality, ranging from parent/offspring bonds to monogamous bonds to trust, empathy, generosity, and social intelligence Caveats: (a) sometimes these neuropeptides are more about sociality than prosociality (in other words, boosting social information gathering, rather than acting prosocially with that information) (b) they most consistently boost prosociality in people who already lean in that direction (e.g., making generous people more generous, while having no effect on ungenerous people) (c) the prosocial effects are within groups, and these neuropeptides can make people crappier to outsiders— more xenophobic and preemptively aggressive. - oxytocin and vasopressin genetics, showing that individuals with genetic variants that result in higher levels of either the hormones or their receptors tend toward more stable monogamous relationships, more actively engaged parenting, better skill at perspective taking, more empathy, and stronger fusiform cortex responses to faces - one oxytocin receptor gene variant is associated with extreme aggression in kids, as well as a callous, unemotional style that foreshadows adult psychopathy - another variant is associated with social disconnection in kids and unstable adult relationships - unfortunately these findings are uninterpretable because no one knows if these variants produce more, less, or the usual amount of oxytocin signaling - having a particular oxytocin receptor gene variant predicts less sensitive mothering— but only when coupled with childhood adversity - Another variant is associated with aggression—but only when people have been drinking - another variant is associated with greater seeking of emotional support during times of stress— among Americans but not Koreans

Transcription Factors

Regulate Genes BUT environment regulates TFs - Short stretch before each gene is called a promoter (ON switch for transcription) - TFs that binds to the promoter's binding site activate the promotor - Both internal and external environments regulate TFs (cellular and extra cellular) - EX - cell needs more glucose -->TF binds to a specific promoter, which activates the gene --> codes for glucose transporters--> get translation via RNA --> More glucose is transported into the cell - EX - mother smells her newborn --> Receptors in the nose active a TF in the hypothalamus --> production of more oxytocin

Modern Evolutionary Synthesis

See image on powerpoint for info

MAO-A Gene/Enviro Interactions - Caspi Study

The authors followed a large cohort of children from birth to age twenty-six, studying their genetics, upbringing, and adult behavior - Did MAO-A variant status predict antisocial behavior in twenty-six-year-olds? No - BUT having the low-activity version of MAO-A tripled the likelihood ONLY in people with a history of severe childhood abuse - It depends on the environment - study is important not just for its demonstration of a powerful gene/environment interaction but for what the interaction is, namely the ability of an abusive childhood environment to collaborate with a particular genetic constitution - In a healthy environment, increased threat sensitivity, poor emotion control and enhanced fear memory in MAOA-L [i.e., the "warrior" variant] men might only manifest as variation in temperament within a 'normal' or subclinical range - However, these same characteristics in an abusive childhood environment—one typified by persistent uncertainty, unpredictable threat, poor behavioral modeling and social referencing, and inconsistent reinforcement for prosocial decision making— might predispose toward frank aggression and impulsive violence in the adult -MAO-A variant/childhood abuse interaction has been frequently replicated, and even demonstrated with respect to aggressive behavior in rhesus monkeys - hints as to how this interaction works —the MAO-A gene promoter is regulated by stress and glucocorticoids - in one study the low-activity MAO-A variant predicts criminality, but only if coupled with high testosterone levels (consistent with that, the MAO-A gene also has a promoter responsive to androgens) - another study low-activity MAO-A participants in an economic game were more likely than high-activity ones to retaliate aggressively when exploited by the other player—but only if that exploitation produced a large economic loss; if the loss was small, there was no difference. - another study low-activity individuals were more aggressive than others—but only in circumstances of social exclusion. - the effects of this genetic variant can be understood only by considering other, nongenetic factors in individuals' lives, such as childhood adversity and adult provocation

Twin Studies

Twin design as an experiment of nature, as well as nurture - Use questionnaires to determine zygosity (MZ and DZ) among twins - Use different phrased questions in different countries and cultures - Design in which genetic and environmental influences on a trait or disease are estimated by contrasting the similarity of MZ and DZ twins - Common misconception that need twins reared apart, but twins reared together are just as useful. Can draw inferences regarding genetic influences from: 1. Difference in correlation between MZs and DZs of some trait 2. The r between MZ twins reared apart 3. Difference in r between reared-apart MZs & DZs Can draw inferences regarding shared environmental influences from: 1. Difference in r between MZs and DZs, specifically the degree to which the DZ twin r is greater than half the MZ twin r Can draw inferences regarding non-shared environmental influences from: 1. Difference in MZ twin r from 1 - you need TONS of QUANTIFICATION to get good estimates from these studies

Twins, Adoptees, and Adopted Twins

Twins Initially, examining twins helped rule out the possibility of genetic determination of a behavior -Suppose one of each pair has schizophrenia; does the twin as well? - If there are any cases where the other twin doesn't , you've shown that the genome and epigenetic profile inherited at birth do not solely determine the incidence of schizophrenia - more elegant twin approach emerged, involving the key distinction between identical (monozygotic, or MZ) twins, who share 100 percent of their genes, and fraternal, nonidentical (dizygotic, or DZ) twins, who, like all other sibling pairs, share 50 percent of their genes - Compare pairs of MZ twins with same-sex DZ twins - each pair is the same age, was raised in the same environment, and shared a fetal environment; the only difference is the percentage of genes shared - Examine a trait occurring in one member of the twin pair; is it there in the other? - if a trait is shared more among MZ than among DZ twins, that increased degree of sharing reflects the genetic contribution to the trait Adoptees - Identify individuals adopted soon after birth. All they share with their biological parents is genes; all they share with their adoptive parents is environment - Thus, if adopted individuals share a trait more with their biological than with their adoptive parents, you've uncovered a genetic influence - research consistently showed that genetics plays a major role in a gamut of domains of behavior, including IQ and its subcomponents (verbal ability, and spatial ability), schizophrenia, depression, bipolar disorder, autism, attention-deficit disorder, compulsive gambling, and alcoholism - strong genetic influences were shown for personality measures related to extroversion, agreeableness, conscientiousness, neuroticism, and openness to experience ( "Big Five" personality traits) - genetic influences also found on degree of religiosity, attitude toward authority, attitude toward homosexuality and propensities toward cooperation and risk taking in games - twin studies showed genetic influences on the likelihood of risky sexual behavior and on people's degree of attraction to secondary sexual characteristics - some social scientists report genetic influences on the extent of political involvement and sophistication - NOT one gene for determining behavior though, genetic influences on behavior often work through very indirect routes, something rarely emphasized

Transposable Elements (transposons)

WRONG - genes inherited from your parents are immutable - McClintock - studying the inheritance of kernel color in maize and found patterns of mutations unexplained by any known mechanism. The only possibility, she concluded, was that stretches of DNA had been copied, with the copy then randomly inserted into another stretch of DNA - Transpositional events rarely produce great outcomes - Plants utilize transposons --> there is a drought; plants can't move to wetter pastures like animals can. Plant "stress" such as drought induces transpositions in particular cells, where the plant metaphorically shuffles its DNA deck, hoping to generate some novel savior of a protein - Mammals have fewer transposons than plants. The immune system is one transposon hot spot, in the enormous stretches of DNA coding for antibodies. A novel virus invades; shuffling the DNA increases the odds of coming up with an antibody that will target the invader - transposons occur in the brain!! - In humans transpositional events occur in stem cells in the brain when they are becoming neurons, making the brain a mosaic of neurons with different DNA sequences --> when you make neurons, that boring DNA sequence you inherited isn't good enough

MAO-A in the Serotonin System

a Dutch family with an MAO-A gene mutation that eliminated the protein - serotonin isn't broken down and accumulates in the synapse - the family was characterized by varied antisocial and aggressive behaviors - studies in which the MAO-A gene was "knocked out" produced the same—elevated serotonin levels in the synapse and hyperaggressive animals with enhanced fear responses - this involved a MUTATION in MAO-A resulting in the complete absence of the protein - focus on low-activity MAO-A variants that produced elevated serotonin levels - People with that variant averaged higher levels of aggression and impulsivity and, when looking at angry or fearful faces, more activation of the amygdala and insula and less activation of the prefrontal cortex - suggests a scenario of more fear reactivity and less frontal capacity to restrain such fear, a perfect storm for reactive aggression - studies showed decreased activation of FC regions during various attentional tasks and enhanced anterior cingulate activity in response to social rejection in such individuals studies where serotonin breakdown products are measured in the body, or where serotonin levels are manipulated with drugs, say that low serotonin = aggression - genetic studies, particularly of MAO-A, say high serotonin = aggression - WHY? - probably is that a drug manipulation lasts for a few hours or days, while genetic variants have their effects on serotonin for a lifetime - (a) The low- activity MAO-A variants don't produce higher synaptic levels of serotonin all that consistently because the 5HTT serotonin re-uptake pump works harder at removing serotonin from the synapse, compensating, and maybe even overcompensating (b) Those variants do produce chronically elevated serotonin levels in the synapse, but the postsynaptic neurons compensate or overcompensate by decreasing serotonin receptor numbers, thereby reducing sensitivity to all that serotonin; there is evidence for that too (auto regulation type) (c) The lifelong consequences of differences in serotonin signaling due to gene variants (versus transient differences due to drugs) produce structural changes in the developing brain - MAO-A gene being X linked and its variants being more consequential in males than females - The effects of MAO-A variants are tiny - There is non-specificity in the sense that MAO-A degrades not only serotonin but norepinephrine as well - High non-specificity in the behavioral effects of the variants - maybe the gene has something to do with the extreme reactive aggression of some family members - biggest reason to reject warrior-gene determinism nonsense is something that should be utterly predictable by now: MAO-A effects on behavior show strong gene/environment interactions

Debates about Twin and Adoption studies

criticized the assumptions in twin and adoption studies, showing that they generally lead to overestimates of the importance of genes 1. Twin studies are premised on MZ and same-sex DZ twin pairs sharing environment equally - "equal environment assumption" (EEA) is simply wrong; starting with parents, MZ twins are treated more similarly than DZ twins, creating more similar environments for them. If this isn't recognized, greater similarity between MZs will be misattributed to genes 2. MZ twins experience life more similarly starting as fetuses - DZ twins are "dichorionic," meaning that they have separate placentas - In contrast, 75 percent of MZ twins share one placenta - Thus most MZ twin fetuses share maternal blood flow more than do DZ twins, and thus are exposed to more similar levels of maternal hormones and nutrients. If that isn't recognized, greater similarity in MZs will be misattributed to genes 3. Adoption studies assume that if a child is adopted soon after birth, she shares genes but no environment with her biological parents. But what about prenatal environmental effects? - eggs and sperm can carry epigenetic changes into the next generation. If these various effects are ignored, an environmentally based similarity between mother and child would be misattributed to genes - epigenetic effects from sperm can be small, BUT prenatal and epigenetic effects from the mother can be huge - traits shared more with biological mothers than with fathers argue against a genetic influence 4. Adoption studies assume that a child and adoptive parents share environment but not genes - adoption agencies prefer to place children with families of similar racial or ethnic background as the biological parents - kids and adoptive parents typically share genes at a higher-than-chance level; if this isn't recognized, a similarity between them will be misattributed to environment 5. Adoptive parents tend to be more educated, wealthier, and more psychiatrically healthy than biological parents - adoptive households show "range restriction," being more homogeneous than biological ones, which decreases the ability to detect environmental effects on behavior CONFOUNDS: Everyone agrees that confounds from prenatal environment, epigenetics, selective placement, range restriction, and assumptions about equal environment are unavoidable - Most of these confounds inflate the perceived importance of genes. - Efforts have been made to control for these confounds and generally have shown that they are of less magnitude than charged by many critics - Crucially, these studies have mostly been about psychiatric disorders, which, while plenty interesting, aren't terribly relevant to the concerns of this book - no one has studied whether these confounds matter when considering genetic influences on, say, people's tendency to endorse their culture's moral rules yet rationalize why those rules don't apply to them today, because they're stressed and it's their birthday

TF Regulation

done by the environment 1. can mean intracellular environment - hardworking neuron is low on energy. This state activates a particular TF, which binds to a specific promoter, which activates the downstream gene - gene codes for a glucose transporter; more glucose transporter proteins are made and inserted into the cell membrane, improving the neuron's ability to access circulating glucose. 2. can mean neighboring environment - including the neuron next door, which releases serotonin onto the neuron in question - Suppose less serotonin has been released lately. Sentinel TFs in dendritic spines sense this, travel to the DNA, and bind to the promoter upstream of the serotonin receptor gene - More receptor is made and placed in the dendritic spines, and they become more sensitive to the faint serotonin signal. 3. can mean far-flung within an organism - A male secretes testosterone, which travels through the bloodstream and binds to androgen receptors in muscle cells - activates a TF cascade that results in more intracellular scaffolding proteins, enlarging the cell (muscle mass increases). 4. can mean the outside world - A female smells her newborn, meaning that odorant molecules that floated off the baby bind to receptors in her nose - receptors activate and (many steps later in the hypothalamus) a TF activates, leading to the production of more oxytocin - Once secreted, the oxytocin causes milk letdown --Genes are regulated by all the incarnations of environment!! --Genes don't make sense outside the context of environment

Chance

driven by Brownian motion (the random movement of particles in a fluid) has big effects on tiny things like molecules floating in cells, including molecules regulating gene transcription - influences how quickly an activated TF reaches the DNA, splicing enzymes bump into target stretches of RNA, and an enzyme synthesizing something grabs the two precursor molecules needed for the synthesis

Reliability of Heritability Measures

scads of behavioral and personality traits have heritability scores of 40 to 60 percent, meaning that genetics explains about half the variability in the trait - nature of research typically INFLATES scores - plant geneticist sits in the desert, studying a particular species of plant - Plants with version A always grow to be one inch tall; version B, two inches; C, three inches - What single fact gives you the most power in predicting a plant's height? Obviously, whether it has version A, B, or C—that explains all the variation in height between plants, meaning 100 percent heritability - twelve thousand miles away in a rain forest, a second plant geneticist is studying a clone of that same plant. And in that environment plants with version A, B, or C are 101, 102, or 103 inches tall, respectively. This geneticist also concludes that plant height in this case shows 100 percent heritability - You can either know which version of gene 3127 it possesses or what environment it is growing in. Which is more useful? Knowing which environment. When you study this plant species in two environments, you discover that heritability of height is miniscule - LARGE POINT!! - Study a gene in only one environment and, by definition, you've eliminated the ability to see if it works differently in other environments (do other environments regulate the gene differently) - thus you've artificially inflated the importance of the genetic contribution - The more environments in which you study a genetic trait, the more novel environmental effects will be revealed, decreasing the heritability score - Scientists study things in controlled settings to minimize variation in extraneous factors and thus get cleaner, more interpretable results—for example, making sure that the plants all have their height measured around the same time of year - inflates heritability scores, because you've prevented yourself from ever discovering that some extraneous environmental factor isn't actually extraneous --*** a heritability score tells how much variation in a trait is explained by genes in the environment(s) in which it's been studied*** - Genes typically still play hefty roles in explaining individual variability, given that any given species lives in a limited range of environments - Humans live in TONS on environments - heritability scores in humans plummet the most when shifting from a controlled experimental setting to considering the species' full range of habitats

Intron

sequence of DNA that is not involved in coding for a protein - non-coding region - NOT expressed in mRNA - removed BEFORE translation - compose 95% of total DNA - here we find the instruction manual for when to transcribe particular genes, the on/off switches for gene transcription - A gene doesn't "decide" when to be photocopied into RNA, to generate its protein - before the start of the stretch of DNA coding for that gene is a short stretch called a promoter - TFs binds to the promoter to activate it - causes the recruitment of enzymes that transcribe the gene into RNA. Meanwhile, other transcription factors deactivate gene