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Genetics and Behaviour.docx

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University of Guelph
PSYC 2410
Elena Choleris

Introduction to Genetics 9/27/2012 4:07:00 PM Introduction to Genetics 1859: Darwin‟s “The Origin of Species”  Fifty years later, the rediscovery of the work of Mendel on inheritances o Mechanisms of action of natural selections o Darwin didn‟t understand (a) why conspecifics differ from one another and (b) how anatomical, physiological and behavioural characteristics are passed through generations Gregor Mendel (1822-1884):  Austrian monk  Gardener monk  garden peas  Observed features of many plants and collected information about how they were transmitted across generations (studied inheritance) Dichotomous Traits: traits that come in 1 of 2 versions and never in combination  E.g. in peas, seed colour (brown, white), seed appearance (rough, smooth), flower colour (purple, white) True Breeding lines: breed individuals of same characteristic studying, produce offspring with same trait generation after generation Gene: trait is carried by sequence of DNA that codes for characteristic, there are two kinds of inherited factors for each dichromatic trait (maternal / paternal) Alleles: different versions of genes for same trait (e.g. blue and brown eyes)  Cross fertilized brown and white peas (true breeds)  Observed that in first generation all offspring were brown  Therefore brown allele is dominant over white allele o Brown  dominant trait (e.g. brown eyes in humans) o White  recessive trait (e.g. blue eyes in humans)  Cross fertilize again  Observed ¾ offspring brown and ¼ white offspring o Challenged view that offspring inherit the traits of their parents With alleles…  Each individual carries two alleles (one from mother and one from father)  Maternal (WW), paternal (BB) o First generation all have one from each (WB) and since brown dominates, peas look brown although all carry one white allele o Second generation, come look like parents (BB and WW) and some look brown but carry one allele of each (BW)  Homozygous: carry the same allele (BB and WW)  Heterozygous: carry one of each allele (BW)  Genotype: the genetic make up (BB, BW, WW etc.)  Phenotype: the observable traits (brown, white etc.) o Behaviour is part of the phenotype and is mediated by genotype  One of two kinds of alleles dominates over the other in heterozygotes  For each dichromatic trait, each organism randomly inherits one of it‟s father‟s two factors and one of it‟s mother‟s two factors Modern Application of Mendel‟s Law 9/27/2012 4:07:00 PM Modern Application of Mendel’s Law  Maintenance and reproduction of lines of gene knockout mice where the non-functional gene is necessary for reproduction  Estrogen and social behaviour  Wild type: normal, nothing done  K: knockout gene  Get mendelian frequency  ¼ estrogen normal, homozygous  ½ estrogen normal, heterozygous  ¼ homozygous knockout for estrogen receptors Genes are segments of DNA on chromosomes.  Most DNA in nucleus, some in mitochondria of cell  DNA that is wrapped up and more condensed are called chromosomes o Packing is done by histones Chromatin = DNA + histones and other nuclear proteins  Round spheres are representing histones Genes – Chromosomes and Reproduction  Chromosome pairs: maternal and paternal (1 copy of each)  Coloured bands in images represent different genes  Pair number: species-specific  Humans: 23 pairs, 46 chromosomes total o Pair 23 – X and Y (sex chromosomes) Sexual Reproduction 9/27/2012 4:07:00 PM Sexual Reproduction Fertilization: 2 gametes (eggs and sperm)  1 zygote  23 pairs of chromosomes from each parent? o Gametogenesis through meiosis o Gametes are haploid (only have half of the normal number of chromosomes) therefore when joined together (2 haploid cells), the zygote has the correct number of chromosomes  Zygote divides through mitosis o DNA duplicates just before mitosis There is more to variability!  Thomas Hunt Morgan (1866-1945) o Crossing over (genetic recombination)  Chromosome pairs are often viewed as cross  Exchange genetic material  Unique spliced together recombinations of maternal and paternal origin (adds variability)  Allowed first gene maps o Mutations  Errors in division o Gene linkage  Closer together genes are, higher likelihood of being carried together  E.g. blonde hair and blue eyes  Can then make inferences about how close genes are on chromosomes Sex Chromosomes and Sex-Linked Traits  Typical chromosomes that come in matched pairs  autosomal chromosomes  Pair of chromosomes that determines sex  sex chromosomes o Female XX o Male XY  Virtually all sex linked traits are controlled by genes on X chromosome because Y is small and carries few genes o Dominant traits are often seen in females o Recessive traits are often seen in males (because only 1 X)  E.g. colour blindness DNA and Gene Expression 9/27/2012 4:07:00 PM DNA and Gene Expression DNA:  Described for the first time by James Dewey Watson and Francis Harry Compton Crick in 1953 in Nature magazine o 1962 on a Nobel Prize in Medicine (soon after discovery)  Double stranded helix  Each strand: a sequence of nucleotide bases (ladder)  Connected by o Phosphate o Deoxyribose  4 bases: o adenine  thymine o guanine  cytosine o bonded together through attraction of nucleotide bases (provides 2 strands that are complements of each other)  Sequence of bases is genetic code DNA Replication:  Prior to mitosis DNA replicates  Product: two identical DNA molecules o Contains one stand from parents DNA and a complementary strand  Repair mechanisms to try and spot / repair problems in replication o If not, mutations (accidental alterations of individual genes)  Has the ability to increase or decrease fitness o Down Syndrome  extra chromosome 21 Gene Expression: Structural Genes (most genes): gene  protein  Code for proteins  DNA opens, transcription, RNA synthesized, mRNA (messenger RNA) o If in coiled structure, genes cannot be read o RNA is formed on template of DNA strand (that is unraveled)  RNA = ribonucleic acid  Uracil instead of thymine and ribose backbone in stead of deoxyribose  Single stranded o Sequence of bases on RNA reflect sequence of bases on DNA o mRNA (RNA strand created) travels outside of nucleus and binds with ribosome  Ribosome moves along mRNA translating genetic code  Proteins are formed by sequence of amino acids  Structure and function of protein is affected by amino acids it is comprised of  Amino acid sequence is dependent on codon (group of 3 sequence of RNA)  As ribosome reads mRNA, it attracts tRNA (transfer RNA that is for the appropriate amino acid molecule) o Translation: tRNA has 2 binding sites (1 for specific amino acid and one for sequences of 3 bases on RNA molecule)  Synthesis of proteins: o DNA  RNA  transcription o RNA  protein  translation Operator Genes (switches)  Control one or more structural genes (regulation)  Enhancers: stretches of DNA whose function is to determine whether particular structural genes initiate the synthesis of proteins and at what rate  Determines how cell will develop and at what rate  Default state either always ON or always off (same for structural genes) o Default OFF  ON, Up regulated OR Down regulated  Not always steady level of expression o Environmental signals  DNA binding proteins (transcription factors) Control of gene expression determines cell type / function / regulation  Influenced by experience and environment  If not controlled, cells would all be the same o Not all genes activity is needed for cell survival at all times or in all cells o All cells in body contain all DNA, but not all are expressed The Central Dogma of Molecular Biology (Francis Crick):  Goes back to the 50s (old)  Problems o Many factors modify gene activity during transcription and translation o Nucleic acids (DNA and RNA) are not only way to store and carry information in cells  After the 50s… o One gene one protein story is not be all end all  More than 1 protein for one gene o Proteins undergo number of chemical modifications that effect how active they are, when they are active, what role they serve o Other factors in RNA (transcription factors)  Human Genome Project (1990-2001) o Make gene map of all 3 billion bases that compose human chromosomes o Humans have small number of genes  20,000 in humans, 20,000 in mice and more in corn Regulation of Gene Expression: Active Nongene DNA  Portions of DNA that did not directly participate in synthesis of proteins o Thought to be nonfunctional  pseudogenes, junk DNA  Now many areas of active nongene DNA are being discovered o Control structural expression Splicing and Alternative Splicing  Not all bases on DNA molecule end up coding for amino acids and impacting structure of protein that gene codes for  2 types of sequences o exons (code for amino acids) o introns (not involved in protein formation)  Splicing: changes to pre-mRNA molecules after transcription o Removal of sequences that are not relevant to protein synthesis (introns)  Alternative splicing: the exons from a single RNA are rearranged in different mRNAs that can code for different proteins / peptides o One gene, many products possible Micro and other Regulatory RNAs  Short (approx. 22 nucleotide bases) RNA molecules  Bind to mRNAs with complementary sequences and affect their translation to proteins  Mostly inhibitory effects (gene silencing), blocking of function, can no longer be translated into proteins o Regulate translation, recent research shows might help translation o Discovery in 2000, big discovery in biology  Huge impact on how genes are expressed in the cell o Selective silencing of a gene  behavioural effects?  Can create synthesized miRNA (equal and complementary) that targets any mRNA you want and blocks function (like what happens naturally, can induce it and study the function of the gene, what is the behavioural outcome?)  Approx. 60% of genes can be regulated by miRNAs (micro RNAs)  Influence brain development, synapse function and disruption has been associated with neurodegenerative disorders  In 2006 won Nobel Prize in Medicine Monoallelic Expression  Many in nervous system  One of 2 alleles is inactivated and by epigenetic mechanisms, the other is expressed o Sometimes depends on whether it was inherited by mother or father Transcription Factors  Go into cell nucleus, bind to DNA and regulate whether gene is transcribed  A protein that either alone or after activation by another molecule (a ligand) up- or down- regulates the transcription of specific genes  Two key aspects: o By the gene: must have a response element (specific sequence of DNA that can bind to this protein) o On the transcription factor: must have a DNA-binding domain (capable of binding to DNA and recognizing element)  Examples of transcription factors: specific proteins needed for DNA duplication (e.g. polymerases) receptors for steroid hormones (e.g. estrogens, progesterone, testosterone, cortisol), receptors for thyroid hormones, vitamin D etc. o All can regulate genes o Why hormones can have wide effects  Co-regulators: other molecules that either activate or inhibit the activity of transcription factors within a transcription complex o Transcription factors very rarely work on their own Epigenetics  Change in phenotype that is heritable but does not involve DNA mutation o Not related to changes in sequences of DNA, gene is expressed differently o Mechanisms that influence expression of genes without changing the genes themselves  Change in phenotype is switch-like o Can be on or off, effects if gene is available for transcription  Change is heritable even if initial conditions that caused the switch disappear  E.g. cellular differentiation o As cell divides, they pass on epigenetic changes to daughter cells and do not go back to undifferentiated cells o If epigenetic change is in germline (sperm and eggs)  Heritable across generations (from parent to offspring) o E.g. butterfly (larva  butterfly, same genes, different phenotypes)  Epigenetics effects of parental care: o Non genetic effect on behaviour that then becomes heritable o Quality of parental care  Increase or decrease stress responses in offspring  Behaviours such as quality of nest, time mother spends with offspring and nursing them, time spent licking and grooming  Test offspring for stress responses (see previous lectures)  Low quality parental care  high stress responses  Then changes parental care given by offspring  See changes if breed offspring from „bad‟ mom and offspring of „good‟ mom  Over multiple generations (nongenomic transmission) Two main components of epigenetic code:  DNA Methylation o Chemical change o Methyl marks added to certain DNA bases represses gene activity  Group to some of the cytosine bases of the DNA  These alter the activity of the DNA wrapped around them (gene transcriptions)  High methylation  reduced transcription (can be silenced for good)  Hard to reverse changes to DNA  Methylation is maintained over cell duplication cycles  When duplicate, corresponding cytosines are methylated o High maternal cares  demethylation of genes involved in the control of stress responses  Gene in stress response is methylated, effects then become blunted  Lower stress hormones  Lower anxiety o Mutation in agouti gene  golden colour and obesity in mice (phenotype) o When pregnant mice are given vitamin B (already transferred genes to offspring)  brown and lean mice  Diet induced methylation of the mutated gene (agouti gene) prevents its expression  Doesn‟t change sequence, changes whether gene is active (mutation does not appear in phenotype)  Environmental regulation of gene expression to change phenotype o Histone Modifications  A combination of different molecules can attach to the „tails‟ of histones  Various modifications: (most common)  Phosphorylation  Acetylation  Most studied  Methylation  Regulate chromatin opening (packaging of DNA, whether it is available for transcription  first step in transcription is to open up coiled DNA)  Open chromatin  transcriptional activation  Closed chromatin  transcriptional repression
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