Genes and Heredity Lecture Notes PDF

Trait variation and categorization, basic models of inheritance, and the connection via DNA Department of Psychology and Neuroscience, Sept 5th, 2024 Ian C.G. Weaver, Ph.D. Human Skull Inscribed by a Phrenologist, 19th century (Franz Joseph Gall) Photograph: Eszter...

Trait variation and categorization, basic models of inheritance, and the connection via DNA Department of Psychology and Neuroscience, Sept 5th, 2024 Ian C.G. Weaver, Ph.D. Human Skull Inscribed by a Phrenologist, 19th century (Franz Joseph Gall) Photograph: Eszter Blahak/Semmelweis Museum The Cerebrum or Cortex is Divided into Four Lobes Opening thoughts… “Nothing in biology makes sense except in the light of evolution” Theodosius Dobzhansky 1900-1975 (1973) “We cannot study a behaviour without understanding the original selection pressures that created the behaviour” Tooby & Cosmides (1994)  Evolution via Natural Selection Charles Darwin & Alfred Wallace The cognitive mechanisms (modules) that constitute the human brain are assumed to have developed via natural selection. Evolutionary theory (devised by Charles Darwin & Alfred Wallace, 1844) consists of several simple principles: 1. 'Principle of Variation': Individuals within a species show variation in their physical and behavioural traits. 2. 'Principle of Inheritance': Some of this variation is heritable. 3. 'Principle of Adaptation': Individuals are in competition with one another for scarce resources and some inherited variations will have survival advantages. 4. 'Principle of Evolution': as a consequence of being better adapted to an environment, some individuals will produce more offspring, who will inherit the same advantages. This is called 'fitness'.  Sexual Selection W. D. Hamilton 1936 - 2000 Darwin was puzzled by the existence of certain physical features that do not contribute to survival, and may even hamper it (e.g., the peacocks tail): He realised that such features were governed by sexual selection - the creation and maintenance of features essential for attracting the opposite sex, and defending one’s status. Natural selection and sexual selection thus work together. William. D. Hamilton (1964) reformulated evolutionary theory by showing that the measure of an individuals direct reproductive success (fitness) was too narrow a concept: He introduced the term ‘inclusive fitness’ - characteristics will be selected for that improve the chances of an individuals genes being passed directly or via relatives. Animal Behaviour: Evolution and Mechanisms The evolutionary process by which some genes in a population spread more than others do, causing species to change over time: Natural Selection the principle that, among the range of inherited trait variations, those that lead to increased reproduction and survival will most likely be passed on to succeeding generations Mutations random errors in gene replication that lead to a change in the sequence of nucleotides in the genome, resulting in changes in specific gene expression, brain function and behaviour Adaptive Behaviour an evolutionary adaptation that enhances survival and reproductive success evolves as natural selection fine-tunes an animal to its environment  Adaptive Problems Animals face a series of adaptive problems in their physical and social environments, e.g., finding a mate; finding food; avoiding predation; fighting off disease. Each of these problems can affect reproductive success (fitness). Each problem has been tackled by adaptive changes in physiology and behaviour. Social scientists accept that our bodies have been sculpted by evolutionary forces, e.g., we all possess sweat glands for thermoregulation. Evolutionary psychologists argue that our psychological mechanisms and the resulting behaviours have also been shaped by the same forces. They attempt to construct plausible arguments as to how our behaviours function as adaptations.  Adaptations: Why does a certain trait exist? Proximate Causation - the immediate psychological, physiological, biochemical and environmental reasons: Sensory systems - need to be able to perceive danger Mechanisms that drive muscles that elicit behaviour - need to be able to contract muscles to run Cellular activities regulate development - nerve function Ultimate Causation - the reason why it increased fitness in the evolutionary past: How does the internal machinery work? Why does machinery work that way? Is that behaviour an adaptation? How does that behaviour allow the individual to survive, find food, find mates, escape predators, communicate?  Not all behaviours are ‘adaptive’ 1941 - 2002 An adaptation represents a trade-off between different survival and reproductive needs (e.g., having a large body) The environment may alter more rapidly than the organism can evolve (e.g., change in diet) An adaptation is not always adaptive in every circumstance (e.g., choking) Not all features are adaptive (e.g., the navel) Stephen Jay Gould (1991) cautioned about the use of 'just-so' stories Features that may once have been adaptive for one function may have changed over time to serve a different function—exaptations or co-option describe a shift in the function of a trait during evolution (e.g. feathers for warmth and then flight) Other features may look like adaptations but in fact are simply design constraints—spandrels are a phenotypic characteristic that is a byproduct of the evolution of another trait, rather than a direct product of adaptive selection  Not all behaviours are ‘adaptive’ 1941 - 2002 https://www.youtube.com/watch?v=YoQIJqoYlIM The surface area between two adjacent arches and the horizontal conice above them  The Role of the Environment David M. Buss Buss et al., (1998) pointed out that the environment can also play a significant role: Interactions with environmental features during development are critical for normal development Input during development may be required in order to activate certain adaptive features (e.g., experience of sexual relationships and jealousy) Developmental events may channel individuals into one of several different paths (e.g., parenting style) Environmental events may disrupt the emergence of an adaptation  Evolutionary Psychology Ernst Haeckel 1834 - 1919 Evolutionary psychology is the study of the physiological, evolutionary and developmental mechanisms of behaviour and experience. i.e., the application of Darwinian principles to the understanding of human nature. A strong emphasis is placed upon brain functioning. Biological explanations of behaviour fall into four categories: Physiological - relates a behaviour to the activity of the brain and other organs. Ontogenetic - describes the development of a structure or behaviour (Ontogeny recapitulates phylogeny). Evolutionary - reconstructs evolutionary history of a behaviour. Functional - describes why a structure or behaviour evolved. Deep understanding of a particular behaviour is tied to being able to explain the behaviour from each of these perspectives. The Brain Size of Humans (and Human Ancestors) has Grown Sharply 3x total capacity Biggest increase = prefrontal cortex Humans can plan behaviours, make decisions, think creatively, control bodily processes etc., to an increased degree—e.g., hunger strike  Phylogeny and Ontogeny of PFC The prefrontal cortex has expanded over mammalian and primate evolution. A greatly enlarged prefrontal cortex is a distinctively human and primate feature. The prefrontal cortex accounts for 29% of total cortex in humans  Function Overview of PFC The functions of the frontal lobes defy a simple definition. They are not invested in any single ready-to-label function. Prefrontal cortex plays the central role in forming goals and objectives and then in devising a plan of action required to attain those goals. It selects the cognitive skills needed to implement the plans, coordinates those skills, and applies them in a correct order. Finally, the prefrontal cortex is responsible for evaluating our actions as success or failure relative to our intentions. Evaluating Evolutionary Psychology Evolutionary psychology approach is just one theory of many: It has its limitations and weaknesses, and its critics e.g., 'deterministic', i.e., ignores the role of the environment in shaping human behaviour. Bidirectional view - environmental and biological conditions influence each other: Evolution gives us bodily structures and biological potentialities, but it does not dictate behaviour Individuals create behaviour in the context of culture  Brain Sizes of Various Primates and Humans in Relation to Length of Juvenile Period Extended childhood period allows time to develop a large brain and learn complexity of human society  The use of some incomprehensible scientific jargon will follow… GENOTYPE & PHENOTYPE  The Father of Genetics: Gregor Mendel (1800s) l Crossed a line bred true for brown seeds with one bred true for white l First generation offspring all had brown seeds l When the first generation were bred, the result was ¾ brown and ¼ white seeds l True-breeding lines l White (ww) l Brown (BB) l Brown was the dominant phenotypic trait, appearing in all of the first generation offspring (Bw) l Phenotype – observable traits l Genotype – traits present in the genes l If the dominant trait is present in the genotype (Bw), it will be observed in the phenotype (brown seeds) Gregor Mendel (1800s) Each inherited factor is a gene Two genes that control the same trait are called alleles Homozygous – 2 identical alleles (BB, ww) Heterozygous – 2 different alleles (Bw)  Genetic Foundations Human life begins as a single cell Nucleus of each cell contains chromosomes: – Chromosomes: thread-like structures made up of DNA – DNA: a complex double-helix molecule that contains genetic information – Genes: units of hereditary information in each chromosome humans have ~25,000 genes genes direct cells to reproduce themselves and to assemble proteins Genes collaborate with each other and with non-genetic factors inside and outside the body Genetic expression is affected by the environment – Proteins: building blocks of cells and regulators that direct the body’s processes  Cells, Chromosomes, Genes, and DNA Chromosomes Cell DNA Nucleus (center of cell) contains Chromosomes are Gene: a segment of chromosomes threadlike DNA (spiraled double and genes structures chain) containing the composed of DNA molecules hereditary code Structural aspects: ~2 m DNA must be fit into ~5-10 µm cell nucleus Physiological aspects: DNA is the same in all somatic cells of an organism. 25,000 Genes è ~140,000 Proteins & different cell types?  Meiosis versus Mitosis All somatic cells in the human body have 46 chromosomes arranged in 23 pairs When a cell divides by way of mitosis, it produces two daughter cells—somatic cells. No recombination/crossing over of chromosomes in prophase Somatic cells are clones of the original cell When a cell divides by way of meiosis, it produces four daughter cells—germ cells. Involves recombination/crossing over of chromosomes in prophase I Germ cells are not clones of the original cell, because each gamete has exactly half as many (i.e., 23) chromosomes as the original cell. Genetic Difference Between Males and Females Fertilization: fusing of sperm and egg to create a zygote – Creates one set of paired chromosomes (23 from each parent) Sex: determined by 23rd pair of chromosomes – XX = female, XY = male – A karyotype (Greek karyon = kernel, seed or nucleus) is the number and appearance of chromosomes in the nucleus of a eukaryotic cell Giemsa, G-banding  Sources of variability: normal development 1. Combining genes of both parents increases genetic variability Chromosomes in zygote are not exact copies 2. Identical (monozygotic) twins develop from a single zygote that splits into two 3. Fraternal (dizygotic) twins develop from separate eggs and sperm 4. Gene mutations can permanently alter segments of DNA  Sources of variability: rare genetic abnormalities Gene-Linked Abnormalities Single gene disorder Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Y-linked Mitochondrial Chromosomal Abnormalities Occur when there is an error in cell division following meiosis or mitosis Caused by a missing, extra, or irregular portion of chromosomal DNA  Behaviour Genetics: how are traits studied? Human behavioural and personality characteristics are observable and measurable components of a person’s phenotype, which is the detectable expression of a person’s genotype interacting with his or her environment Behaviour Genetics seeks to discover the influence of heredity and environment on individual differences in human traits and development Linkage studies look for patterns of inheritance of genetic markers in large families. A genetic marker is a segment of DNA that varies among individuals.  Heritability and the Genetics of Difference Heritability is the statistical estimate of the proportion of the total variance in some trait that is attributable to genetic differences among individuals within a group. - Expressed as proportion (e.g., 0.60 or 60/100). - Maximum value is 1.0. - some variables such as height are highly heritable (0.8), other variables such as musical ability (0.2) are moderately heritable. Limitations: 1. An estimate of heritability applies only to a particular group living in a particular environment. 2. Heritability estimates do not apply to individuals, only to variations within a group. 3. Even highly heritable traits can be modified by the environment.  Determining Heritability The heritability of a behaviour is estimated in three ways: 1) Examining whether children more closely resemble their adoptive or biological parents 2) Comparing monozygotic (identical) and diozygotic (fraternal) twins 3) Examining identical twins raised in different households (social environments)  1. Adoption studies Studying adopted children allows researchers to compare correlations between the traits of adopted children and those of their biological and adoptive relatives. These results are used to estimate heritability. 2. Identical vs. non-identical twin studies  3. Twin’s raised in different environments Identical twins raised apart from each other are of special interest because they have identical genes but a different environment. Any similarities in traits between identical twins who were separated early in life and reared apart should be primarily genetic and should permit a direct estimate of heritability.  Shared and Non-shared Environmental Experiences Shared environmental experiences: Siblings’ common experiences – Parents’ personalities – Intellectual orientation – Family’s socioeconomic status – Neighborhood – Shared environment accounts for little of the variation in children’s personality or interest Non-shared environmental experiences: the child’s unique experiences – Within family – Outside family – Not shared by another sibling – Heredity influences the non-shared environments through heredity– environment correlations  Heredity-Environment Correlations Heredity-environment interaction has complexities Individuals influence environments, yet individuals ‘inherit’ environments Genotype-environment correlations change as children grow For example: Parents provide When genotype elicits When children seek rearing environment certain types of physical out compatible and social environments and stimulating environments Searr & McCartney, Child Devel. 1983 Genes & Individual Differences: e.g., Intelligence Intelligence Quotient (IQ) - A measure of intelligences originally computed by dividing a person’s mental age by his or her chronological age and multiplying the result by 100 - It is derived from norms provided for standard intelligence tests Genetic influence grows even stronger with age:.50 for children and adolescents.60 -.80 for adults Intelligence scores of identical twins raised together are always more highly correlated (87%) than for fraternal twins The scores of adopted children are highly correlated with their biological parents  Genetic Influences: Heritability of Various Human Attributes The role of genetic factors is shown by the extent to which identical twins are more similar to each other than are fraternal twin pairs  MZ and DZ Concordance Rates of Psychiatric Disorders Psychiatric diseases are complex diseases that aggregate in families but do not segregate in a simple Mendelian manner. Molecular genetic studies, have been able to explain only a very small fraction (1-2%) of heritability, a sharp contrast with population estimates of 30-80% heritability of these diseases. Epidemiological studies have demonstrated correlations between life experiences (pre- and/or perinatal events, socioeconomic status, etc.) and psychiatric disease risk, but are unable to detect any specific causal environmental hazards.  Prevalence and Incidence 1) Both prevalence and incidence are measures of distribution of a disease in a population. 2) Prevalence is a measure of the number of cases of a disease in a certain population for a specific period of time while incidence is a measure of the number of new cases of the disease. 3) Prevalence is used to refer to how widespread a disease has become while incidence is used to refer to the rate at which the disease is manifested in a certain population. 4) Prevalence takes into consideration both the number of old and new cases of a disease as well as their duration while incidence only takes into consideration the number of new cases. 5) Compared to prevalence, incidence is more reliable in determining the risk of a certain disease to a population.  Complex (or Multifactorial) Disorders Some disorders, such as sickle cell disease and cystic fibrosis, are caused by mutations in a single gene. However, many disorders, such as heart disease, diabetes, Alzheimer disease, autism, Parkinson disease, asthma, and spina bifida do not have a single genetic cause—they are likely associated with the effects of multiple genes (polygenic) in combination with lifestyle and environmental factors and referred to as complex (or multifactorial disorders). Although complex disorders tend to run in families, unlike single gene disorders, they do not have clear-cut patterns of inheritance, so it is difficult to predict a person’s risk of inheriting or passing on these diseases. Because they can be caused by genetic and environmental factors, complex disorders can be difficult to treat. Weaver, I.C.G. 2014 Advances in Genetics 86, 277-307.  Missing Heritability of Complex Disorders The discrepancy between epidemiological heritability estimates and the proportion of phenotypic variation explained by DNA sequence differences is referred to as the ‘missing heritability’. Several theories to explain this unaccounted heritability: part of heritability being ‘hidden’ in numerous weakly contributing genetic risk factor patterns of linkage disequilibrium—i.e., the nonrandom occurrence of a combination of alleles or genetic markers in a population heritability estimates being inflated by epistatic gene interactions—i.e., genes can mask each other's presence or combine to produce an entirely new trait Weaver, I.C.G. 2014 Advances in Genetics 86, 277-307.  Missing Heritability and major psychosis Given the large unaccounted heritability of major psychosis (collective term for MDD, SCZ and BPD), other molecular mechanisms may be involved: passage of epigenetic marks (e.g., DNA/histone modification) through the germ line passage of maternal RNA molecules into the embryo potential passage of prion proteins from parent to offspring biochemical state of the gametes at the time of conception transmission of nutrients, bacteria, or antibodies from maternal circulation to that of the offspring All of these factors can, and do, influence phenotypic variability during development. Weaver, I.C.G. 2014 Advances in Genetics 86, 277-307.  Context: Linking Environment to Genes, Brain Development, and Plasticity Not all traits are equally heritable or unaffected by shared environments Some studies may underestimate the impact of the environment Even traits that are highly heritable are not rigidly fixed and can be modified by experience. Genetic influence on IQ grows even stronger with age Experiences that hinder cognitive performance - Poor prenatal care - Malnutrition - Exposure to toxins - Stressful family circumstances Experiences that enhance cognitive performance - Good health care and nutrition - Mental enrichment in home and child care or school Weaver, I.C.G. 2014 Advances in Genetics 86, 277-307.  Conclusions Phenotypic Traits are defined as habitual patterns of behavior, thought, and emotion, which involves the expression of genes. The relative contributions of heredity (the passing of traits to offspring from its parents or ancestor) and environment are not additive Complex behaviours (traits, behavior styles and patterns) have some genetic loading that provide an individual with a risk for a particular developmental outcome Our environment is complex, and the interaction of heredity and environment is extensive Much needs to be learned about specific ways in which genetics and environment interact to influence development If, Gene x Environment Interactions (from a developmental perspective) = Phenotype, then what is the interface x?