BIOL 1P91 - Chapter 18 Student 2024 PDF

Epigenetics, Linkage, and Extranuclear Inheritance Chapter 18 1  Chapter 18 Outline  Overview of Epigenetics  Epigenetics I: Genomic Imprinting  Epigenetics II: X-Chromosome Inactivation  Epigenetics III: Effects of E...

Epigenetics, Linkage, and Extranuclear Inheritance Chapter 18 1  Chapter 18 Outline  Overview of Epigenetics  Epigenetics I: Genomic Imprinting  Epigenetics II: X-Chromosome Inactivation  Epigenetics III: Effects of Environmental Agents  Extranuclear Inheritance: Organelle Genomes  Genes on the Same Chromosome: Linkage and Recombination 2  Introduction  Mendelian inheritance patterns follow three rules: 1. Genes are passed unaltered from cell to cell, and from generation to generation 2. The genes obey Mendel’s law of segregation 3. Crosses with more than two genes obey Mendel’s law of independent assortment  Here we will examine deviations from these rules, due to: 1. Epigenetics 2. Genetic material that is located outside of the nucleus 3. Genes located on the same chromosome 3  Epigenetics  Gene expression: DNA  RNA  Protein  DNA mutations can affect a phenotype by altering the RNA or protein that is produced  Similarly, changes in gene expression can affect a phenotype by altering the amount of RNA & protein that is produced  Transient increases or decreases in gene expression due to environmental signals = gene regulation  Epigenetic gene regulation = Stable changes in gene expression that are passed from cell to cell and are reversible, but do not involve a change in the sequence of DNA  Epi- = “over” ClickOverview 18.1 to edit Master text of epigenetics 4  Example: Human cell types  All cells in the human body contain the same DNA but exhibit very different features/phenotypes  For example, muscle cells express high levels of actin and myosin, which are important for muscle contraction  As muscle cells develop in an embryo, epigenetic changes ensure that these genes are turned ON  In contrast, genes that are specific to other cell types (e.g. nerve cells, liver cells) would undergo epigenetic silencing to be turned OFF in muscle cells  These epigenetic changes are established in the developing embryo, and are passed from cell to cell to ensure stable gene expression patterns in the adult 5  Example: Vernalization  Many species of flowering plants undergo vernalization  Process in which cold temperatures are required to flower  Flowering requires low levels of FLC gene expression  In winter, cold temperatures include epigenetic silencing of FLC  These changes are maintained until flowering  After flowering, the epigenetic changes are reversed, FLC expression increases, and flowering is prevented until the next season 6  Epigenetic Inheritance  Some types of epigenetic changes are passed from parent to offspring via the sperm or egg cells  If an epigenetic state is inherited from parents = epigenetic inheritance  However, most epigenetic changes are not inherited  E.g. exposure to cigarette smoke can induce epigenetic changes in the lung cells  These changes can be stable and passed from cell to cell, and eventually lead to cancer development  7  X Inactivation  In female mammals, one X chromosome is inactivated at random in all somatic cells in the early embryo  Silencing is epigenetic: Chromosome is marked & condensed, preventing gene expression  Condensed X is visible as a Barr body  Originally observed in cells of female Expressed X Barr body (condensed X) cats, but not males ClickX-Chromosome 18.3 to edit Master text Inactivation 8  Calico Cats  Gene for coat colour is on the X chromosome  Two alleles: Orange XO and black XB  Calicos are XO XB heterozygous females  One of these two X chromosomes is randomly inactivated in all somatic cells in the early embryo  Produces patches of cells that are orange (XB inactivated) and black (XO inactivated)  Mosaic: an individual with somatic cells that are genetically different from each other 9 10  X Inactivation  X inactivation is a mechanism of dosage compensation  Achieves equal levels of expression of X- linked genes in male and female cells  Mammalian cells have molecular mechanisms to assess the number of X chromosomes and inactivate all but one 11  Extranuclear Inheritance  Transmission of genes that are located outside the cell nucleus  Also called cytoplasmic inheritance  Mitochondria and chloroplasts contain their own genomes  = organelle genomes  Organelle genomes are typically inherited maternally  Egg cell provides most of the cytoplasm, while the much smaller male gamete provides only a nuclear genome ClickExtranuclear 18.5 to edit Master text Inheritance: Organelle Genomes 12  Example: Leaf Colour  Mutations in the chloroplast genome can affect chlorophyll synthesis, affecting leaf colour  Green = normal chlorophyll  White = mutation that prevents most chlorophyll synthesis  Variegated (green/white patches) = a mixture of normal and mutant chloroplasts  Transmission of leaf pigmentation in four-o’ clock plants was observed to not obey Mendel’s law of segregation  Depended solely on pigmentation of maternal parent 13 14 15  Mitochondrial Genomes  Mitochondrial genome of many mammals contains 37 genes  24 genes encode tRNAs and rRNA needed for translation inside mitochondrion  13 genes encode proteins for oxidative phosphorylation  Mutations in human mitochondrial genes can cause a variety of rare diseases that are inherited maternally  Usually result in chronic degenerative disorders that affect brain, eyes, heart, muscle, kidney, and endocrine glands  Organs that require high levels of ATP  A male who is affected with a mitochondrial disease cannot pass the disease to his offspring 16  Example: LHON  Leber’s hereditary optic neuropathy is an inherited form of vision loss  Caused by mutations in mitochondrial genes encoding electron transport proteins  Results in reduced ATP production and death of cells in the optic nerve  Males can inherit the disease from their mother, but cannot transmit the disease to their offspring  Individuals with a mixture of normal & mutant mitochondria, will typically only exhibit disease symptoms if the mutation load is >~60-75% 17  Gene Linkage  When different genes are close together on the same chromosome, they tend to be transmitted as a unit  = Gene linkage  A group of genes that usually stay together during meiosis = a linkage group  Linked genes do not follow the law of independent assortment ClickGenes 18.6 to editon Master text Chromosome the Same 18  Feature Investigation Bateson & Punnett’s Crosses  The first study showing linkage between two different genes was carried out by Bateson and Punnett in 1911  Using a two factor cross involving flower colour and pollen shape in sweet peas, they observed a surprising result:  Purple flowers, long pollen x Red flowers, round pollen produced all purple flowers, long pollen in the F1 generation (as expected)  However, in the F2 generation, they observed far more parental phenotypes than expected 19  Bateson and Punnett did not know why the genes weren’t assorting independently 20  Morgan’s Fruit Flies  Morgan observed a similar deviation from expected ratios in Drosophila  Connected his data to the crossover configurations observed with chromosomes in meiosis and proposed three ideas:  When different genes are located on the same chromosome, the traits determined by these genes are more likely to be inherited together  Due to crossing over during meiosis, homologous chromosomes can create new combinations of alleles  The likelihood of crossing over between two genes depends on the distance between two genes 21 22  Linked Genes  When genes are located close together on the same chromosome, the most abundant phenotypes in the F2 generation will be those with the same combination of traits as the P generation  Nonrecombinants or parental types: Offspring's combination of traits has not changed from parental generations  No crossing over between genes in the F1 gametes  Recombinants or nonparental types: Offspring that have a different combination of traits from parental generation  Crossing over has occurred in the F1 gametes 23  Linkage Mapping  Recombination frequencies provide a method for mapping genes along chromosomes  Recombination occurs less frequently between genes that are close together on the chromosome  Genetic mapping estimates the arrangement and relative distances between linked genes based recombination frequencies  A genetic map shows the linear order of genes along a chromosome 24  Genetic Linkage Map  By 1915 Morgan’s group had mapped 85 mutant genes in Drosophila to four chromosomes  Distance in map units corresponds to the recombination frequency in test crosses  Recombination frequency = Number of recombinant offspring / total offspring * 100  1% = 1 map unit (mu) or centiMorgan (cM) 25  Example  Testcross between body colour and wing shape produced 270 recombinants (133 + 137) out of 1000  Recombination frequency = 270/1000 x 100 = 27 %  Distance between the two genes = 27.0 map units 26