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CAMPBELL BIOLOGY IN FOCUS Urry • Cain • Wasserman • Minorsky • Jackson • Reece Chapters 16 and 17 Lecture Presentations by Kathleen Fitzpatrick and Nicole Tunbridge © 2014 Pearson Education, Inc. Cell differentiation is the process by which cells become specialized in structure and function The physical processes that give an organism its shape constitute morphogenesis Differential gene expression results from genes being regulated differently in each cell type © 2014 Pearson Education, Inc. Cytoplasmic Determinants and Inductive Signals Cytoplasmic determinants are maternal substances in the egg that influence early development As the zygote divides by mitosis, the resulting cells contain different cytoplasmic determinants, which lead to gene expression © 2014 Pearson Education, Inc. The other major source of developmental information is the environment around the cell, especially signals from nearby embryonic cells In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells © 2014 Pearson Education, Inc. Figure 16.3 (a) Cytoplasmic determinants in the egg (b) Induction by nearby cells Unfertilized egg Sperm Early embryo (32 cells) Nucleus Fertilization Zygote (fertilized egg) Mitotic cell division Two-celled embryo © 2014 Pearson Education, Inc. Molecules of two different cytoplasmic determinants NUCLEUS Signal transduction pathway Signal receptor Signaling molecule (inducer) Differentiation of Cell Types Determination is understood in terms of molecular changes, the expression of genes for tissuespecific proteins The first evidence of differentiation is the production of mRNAs for these proteins © 2014 Pearson Education, Inc. Apoptosis: Programmed Cell Death Apoptosis is the best-understood type of “programmed cell death” While most cells are differentiating in a developing organism, some are genetically programmed to die Apoptosis also occurs in the mature organism in cells that are infected, damaged, or at the end of their functional lives © 2014 Pearson Education, Inc. To initiate apoptosis, DNA is broken up and organelles and other cytoplasmic components are fragmented These vesicles are then engulfed by scavenger cells © 2014 Pearson Education, Inc. It is essential to development and maintenance in all animals In vertebrates, it is essential for normal nervous system development and morphogenesis of hands and feet © 2014 Pearson Education, Inc. Figure 16.6 1 mm Interdigital tissue Cells undergoing apoptosis Space between digits © 2014 Pearson Education, Inc. Pattern Formation: Setting Up the Body Plan Pattern formation is the development of a spatial organization of tissues and organs In animals, pattern formation begins with the establishment of the major axes Positional information, the molecular cues control pattern formation. They tell a cell its location relative to the body axes and to nearby cells © 2014 Pearson Education, Inc. Pattern formation has been extensively studied in the fruit fly Drosophila melanogaster Researchers have discovered developmental principles common to many other species, including humans © 2014 Pearson Education, Inc. Figure 16.7a Head Thorax Abdomen 0.5 mm Dorsal BODY Anterior AXES Left Posterior Ventral (a) Adult © 2014 Pearson Education, Inc. Right Drosophila Fruit flies and other arthropods have a modular structure, composed of an ordered series of segments In Drosophila, cytoplasmic determinants in the unfertilized egg determine the axes before fertilization © 2014 Pearson Education, Inc. The Drosophila eggs develop in the female’s ovary, surrounded by ovarian cells called nurse cells and follicle cells After fertilization, embryonic development results in a segmented larva © 2014 Pearson Education, Inc. Figure 16.7 Head Thorax Abdomen 0.5 mm Follicle cell 1 Egg Nucleus developing within ovarian follicle Egg Nurse cell Dorsal BODY Anterior AXES Left Right Egg shell 2 Unfertilized egg Posterior Depleted nurse cells Ventral Fertilization Laying of egg (a) Adult 3 Fertilized egg Embryonic development 4 Segmented embryo 0.1 mm Body segments 5 Larval stage (b) Development from egg to larva © 2014 Pearson Education, Inc. Hatching Genetic Analysis of Early Development: Scientific Inquiry Edward B. Lewis, won a Nobel Prize in 1995 for decoding pattern formation in Drosophila Lewis discovered the homeotic genes, which control pattern formation in late embryo, larva, and adult stages © 2014 Pearson Education, Inc. Axis Establishment Maternal effect genes code cytoplasmic determinants that initially establish the axes of the body of Drosophila These maternal effect genes are also called eggpolarity genes because they control orientation of the egg and consequently the fly © 2014 Pearson Education, Inc. Bicoid: A Morphogen Determining Head Structures One maternal effect gene, the bicoid gene, affects the front half of the body An embryo whose mother has no functional bicoid gene lacks the front half of its body and has duplicate posterior structures at both ends © 2014 Pearson Education, Inc. Figure 16.9 Head Tail T1 T2 T3 A8 A1 A2 A3 A4 A5 A6 Wild-type larva Tail 250 m Tail A8 A7 A6 A7 Mutant larva (bicoid) © 2014 Pearson Education, Inc. A7 A8 It is suggested that the product of the mother’s bicoid gene is concentrated at the future anterior end and is required for setting up the anterior end of the fly Gradients of substances called morphogens establish an embryo’s axes and other features © 2014 Pearson Education, Inc. The bicoid mRNA is highly concentrated at the anterior end of the embryo After the egg is fertilized, the mRNA is translated into Bicoid protein, which diffuses from the anterior end this results in a gradient of bicoid protein Injection of bicoid mRNA into various regions of an embryo results in the formation of anterior structures at the site of injection © 2014 Pearson Education, Inc. Figure 16.10 100 m Results Anterior end Fertilization, translation of bicoid mRNA Bicoid mRNA in mature unfertilized egg Bicoid protein in early embryo Bicoid mRNA in mature unfertilized egg Bicoid protein in early embryo © 2014 Pearson Education, Inc. Bicoid and Pattern Formation © 2014 Pearson Education, Inc. The bicoid research is important for three reasons It identified a specific protein required for some early steps in pattern formation It increased understanding of the mother’s role in embryo development A key principle, that a gradient of molecules can determine polarity and position in the embryo © 2014 Pearson Education, Inc. Cloning Plants and Animals Single differentiated cells from the root of carrot plants in culture medium were able to grow into complete adult plants This work showed that differentiation is not necessarily irreversible Cells that can give rise to all the specialized cell types in the organism are called totipotent © 2014 Pearson Education, Inc. Experiments with frog embryos showed the older the donor nucleus, the lower the percentage of normally developing tadpoles John Gurdon concluded from this work that nuclear potential is restricted as development and differentiation proceeds © 2014 Pearson Education, Inc. Figure 16.11 Experiment Frog egg cell Frog embryo Frog tadpole UV Results Less differentiated cell Fully differentiated (intestinal) cell Donor nucleus transplanted Donor nucleus transplanted Enucleated egg cell Egg with donor nucleus activated to begin development Most develop into tadpoles. © 2014 Pearson Education, Inc. Most stop developing before tadpole stage. Reproductive Cloning of Mammals In 1997, Scottish researchers announced the birth of Dolly, a lamb cloned from an adult sheep by nuclear transplantation from a differentiated cell © 2014 Pearson Education, Inc. Figure 16.12 Technique Mammary cell donor 1 Egg cell donor 2 Nucleus removed Cultured mammary cells 3 Cells fused Cell cycle arrested, causing cells to dedifferentiate 4 Grown in culture Egg cell from ovary Nucleus from mammary cell Early embryo 5 Implanted in uterus of a third sheep Surrogate mother 6 Embryonic development Results © 2014 Pearson Education, Inc. Lamb (“Dolly”) genetically identical to mammary cell donor Since 1997, cloning has been demonstrated in many mammals, including mice, cats, cows, horses, mules, pigs, and dogs Cloned animals do not always look or behave exactly the same as their “parent” © 2014 Pearson Education, Inc. Figure 16.13 © 2014 Pearson Education, Inc. Faulty Gene Regulation in Cloned Animals In most nuclear transplantation studies, only a small percentage of cloned embryos have developed normally to birth Many cloned animals exhibit defects due to Faulty Gene Regulation Epigenetic changes must be reversed in the nucleus from a donor animal in order for genes to be expressed or repressed appropriately for early stages of development © 2014 Pearson Education, Inc. Stem Cells of Animals A stem cell is a relatively unspecialized cell that can reproduce itself indefinitely and differentiate into specialized cells of one or more types Stem cells isolated from early embryos at the blastocyst stage are called embryonic stem (ES) cells; these are able to differentiate into all cell types The adult body also has stem cells, which replace non-reproducing specialized cells (Adult Stem Cells) © 2014 Pearson Education, Inc. Figure 16.14 Stem cell Cell division Stem cell and Fat cells © 2014 Pearson Education, Inc. Precursor cell or Bone cells or White blood cells Figure 16.15 Embryonic stem cells Cells that can generate all embryonic cell types Adult stem cells Cells that generate a limited number of cell types Cultured stem cells Different culture conditions Liver cells Nerve cells Blood cells Different types of differentiated cells © 2014 Pearson Education, Inc. ES cells are pluripotent, capable of differentiating into many cell types Researchers are able to reprogram fully differentiated cells to act like ES cells using retroviruses Cells transformed this way are called iPS, or induced pluripotent stem cells © 2014 Pearson Education, Inc. Cells of patients suffering from certain diseases can be reprogrammed into iPS cells for use in testing potential treatments In the field of regenerative medicine, a patient’s own cells might be reprogrammed into iPS cells to potentially replace the nonfunctional (diseased) cells © 2014 Pearson Education, Inc. Abnormal regulation of genes that affect the cell cycle can lead to cancer The gene regulation systems that go wrong during cancer are the same systems involved in embryonic development © 2014 Pearson Education, Inc. Types of Genes Associated with Cancer Cancer research led to the discovery of cancercausing genes called oncogenes in certain types of viruses The normal version of such genes, called protooncogenes, code for proteins that stimulate normal cell growth and division An oncogene arises from a genetic change leading to either an increase in the amount or the activity of the protein product of the gene © 2014 Pearson Education, Inc. Proto-oncogenes can be converted to oncogenes by: 1. Movement of the oncogene to a position near an active promoter, which may increase transcription 2. Amplification, increasing the number of copies of a proto-oncogene 3. Point mutations in the proto-oncogene or its control elements, causing an increase in gene expression © 2014 Pearson Education, Inc. Figure 16.16 Proto-oncogene Translocation or transposition: gene moved to new locus, under new controls Proto-oncogene Proto-oncogene Gene amplification: multiple copies of the gene Point mutation: New Oncogene promoter Normal growthstimulating protein in excess © 2014 Pearson Education, Inc. Normal growthstimulating protein in excess within a control element within the gene Oncogene Oncogene Normal growthstimulating protein in excess Hyperactive or degradationresistant protein Tumor-suppressor genes encode proteins that help prevent uncontrolled cell growth Mutations that decrease protein products of tumorsuppressor genes may contribute to cancer onset Tumor-suppressor proteins Repair damaged DNA Control cell adhesion Inhibit the cell cycle © 2014 Pearson Education, Inc. Interference with Cell-Signaling Pathways Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers Mutations in the ras gene can lead to production of a hyperactive Ras protein and increased cell division © 2014 Pearson Education, Inc. Suppression of the cell cycle can be important in the case of damage to a cell’s DNA; p53 prevents a cell from passing on mutations due to DNA damage Mutations in the p53 gene prevent suppression of the cell cycle “ Guardian of the Genome” © 2014 Pearson Education, Inc. Figure 16.17 1 Growth factor 3 G protein Ras GTP 2 Receptor 5 NUCLEUS Transcription factor (activator) 6 Protein that NUCLEUS Transcription factor (activator) Overexpression of protein stimulates the cell cycle 4 Protein kinases MUTATION Ras GTP Ras protein active with or without growth factor. © 2014 Pearson Education, Inc. Figure 16.18 2 Protein kinases NUCLEUS Protein that inhibits the cell cycle UV light 1 DNA damage in genome UV light 3 Active form of p53 MUTATION DNA damage in genome © 2014 Pearson Education, Inc. Defective or missing transcription factor Inhibitory protein absent Inherited Predisposition and Other Factors Contributing to Cancer Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes Inherited mutations in the tumor-suppressor gene adenomatous polyposis coli (APC) are common in individuals with colorectal cancer Mutations in the BRCA1 or BRCA2 gene are found in at least half of inherited breast cancers, and tests using DNA sequencing can detect these mutations © 2014 Pearson Education, Inc. DNA breakage can contribute to cancer, thus the risk of cancer can be lowered by minimizing exposure to agents that damage DNA, such as UV Radiation, Toxins and chemicals found in cigarette smoke Viruses play a role in about 15% of human cancers by donating an oncogene to a cell, disrupting a tumor-suppressor gene, or converting a proto-oncogene into an oncogene ( HPV ) © 2014 Pearson Education, Inc. Virus: A Borrowed Life A virus is an infectious particle consisting of little more than genes packaged into a protein coat They live off of cells that already exist © 2014 Pearson Education, Inc. Figure 17.1 0.25 m © 2014 Pearson Education, Inc. Viruses are not cells but are a nucleic acid enclosed in a protein coat © 2014 Pearson Education, Inc. Viral Genomes Viral genomes may consist of either Double or Single-stranded DNA Double- or single-stranded RNA Depending on its type of nucleic acid, a virus is called a DNA virus or an RNA virus © 2014 Pearson Education, Inc. Capsids and Envelopes A capsid is the protein shell that encloses the viral genome A capsid can have various structures © 2014 Pearson Education, Inc. Bacteriophages, also called phages, are viruses that infect bacteria Phages have an elongated capsid head that encloses DNA A protein tail piece attaches the host and injects the phage DNA inside © 2014 Pearson Education, Inc. their the phage to Viruses replicate only in host cells Viruses are obligate intracellular parasites, which means they can replicate only within a host cell Each virus has a host range, a limited number of host cells that it can infect West Nile Measles © 2014 Pearson Education, Inc. Replicative Cycles of Phages Phages are the best understood of all viruses Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle © 2014 Pearson Education, Inc. The Lytic Cycle The lytic cycle is a phage replicative cycle that culminates in the death of the host cell The lytic cycle produces new phages and lyses the host’s cell wall, releasing the more viruses A phage that reproduces only by the lytic cycle is called a virulent phage © 2014 Pearson Education, Inc. Figure 17.4-5 1 Attachment 2 Entry of phage 5 Release DNA and degradation of host DNA Phage assembly 4 Assembly Head Tail Tail fibers © 2014 Pearson Education, Inc. 3 Synthesis of viral genomes and proteins The Lysogenic Cycle The lysogenic cycle replicates the phage genome without destroying the host The viral DNA molecule is incorporated into the host cell’s chromosome This integrated viral DNA is known as a prophage © 2014 Pearson Education, Inc. Figure 17.5b Daughter cell with prophage Many cell divisions create many infected bacteria. Prophage exits chromosome. Lysogenic cycle Prophage Prophage is copied with bacterial chromosome. Phage DNA integrates into bacterial chromosome. © 2014 Pearson Education, Inc. Animation of Cycles © 2014 Pearson Education, Inc. Animal Virus and Viral Envelopes An animal virus with an envelope uses it to enter the host cell that help them infect the © 2014 Pearson Education, Inc. RNA as Viral Genetic Material Retroviruses use reverse transcriptase to copy their RNA genome into DNA HIV (human immunodeficiency virus) is the retrovirus that causes AIDS (acquired immunodeficiency syndrome) © 2014 Pearson Education, Inc. Viral DNA that is integrated into the host genome is called a provirus Unlike a prophage, a provirus is a permanent resident of the host cell © 2014 Pearson Education, Inc. Figure 17.7b HIV Membrane of white blood cell 0.25 m HIV entering a cell © 2014 Pearson Education, Inc. New HIV leaving a cell Emerging Viruses Viruses that suddenly become apparent are called emerging viruses HIV is a classic example The West Nile virus appeared in North America first in 1999 and has now spread to 48 states © 2014 Pearson Education, Inc. Three processes contribute to the emergence of viral diseases The mutation of existing viruses, which is especially high in RNA viruses Dissemination of a viral disease from a small, isolated human population, allowing the disease to go unnoticed before it begins to spread Spread of existing viruses from animal populations; about three-quarters of new human diseases originate this way © 2014 Pearson Education, Inc. Figure 17.8 1 m (a) 2009 pandemic H1N1 influenza A virus © 2014 Pearson Education, Inc. (b) 2009 pandemic screening A vaccine is a harmless derivative of a pathogen that stimulates the immune system to mount defenses against the harmful pathogen Vaccines can prevent certain viral illnesses Viral infections cannot be treated by antibiotics Antiviral drugs can help to treat, though not cure, viral infections © 2014 Pearson Education, Inc.