2.1 Viruses and the Origins of Life on Earth.pdf

2.1 Viruses and the Origins of Life on Earth Viruses Tiny, infectious particle that can only reproduce by infecting a host cell Can be thought of as obligate, intracellular parasites Are not living organisms: They are “acellular” (no cells) They lack a metabolism and do not grow. They depend on host...

2.1 Viruses and the Origins of Life on Earth Viruses Tiny, infectious particle that can only reproduce by infecting a host cell Can be thought of as obligate, intracellular parasites Are not living organisms: They are “acellular” (no cells) They lack a metabolism and do not grow. They depend on host cells to make copies of themselves. Their origin is uncertain. They can infect nearly all life forms. They are not only species specific but tissue specific Viruses were known to exist long before they could be seen 1884: development of porcelain filter able to remove bacteria 1886: tobacco mosaic disease was shown to be infectious 1892: disease could still be transmitted even after filtration The tobacco mosaic virus, seen here by transmission electron microscopy (left), was the first virus to be discovered. The virus causes disease in tobacco and other plants, such as the orchid (right). Virus Size and Imaging Almost all viruses are too small to be seen with light microscopes. A single virion may be only 20 nm across. The invention of electron microscopes in the 1930s led to the discovery of many types of viruses in many types of organisms. In these transmission electron micrographs, (a) a virus is as dwarfed by the bacterial cell it infects, as (b) these E. coli cells are dwarfed by cultured colon cells. Virus Evolution No single common ancestor of all viruses! Regressive hypothesis: the “devolution” from free-living cells Progressive hypothesis: nucleic acid molecules “escaped” from cells Virus first hypothesis: the first self-replicating molecules No significant evidence for any of the hypotheses. Virus Morphology A virion has: Nucleic acid core: DNA (double stranded or single stranded) or RNA Protein capsid coating protecting the genetic material Most have glycoproteins that help the virus attach to host cell Some have an outer envelope Some have additional proteins such as enzymes The complexity of the host does not necessarily correlate with the complexity of the virion. Capsid Structure The capsid is made up of many protein molecules called capsomeres ○ Enveloped: capsid encased in lipid bilayer membrane from host cell ○ Encoded by the virus genome, not host cell Virus attachment proteins are encoded by virus genome Naked: lack membrane Capsid Shape Made up of capsomeres Helical Icosahedral Complex ○ ○ Head-tail “blob” Virus Genomes The virus core contains the genome. either DNA or RNA (but not both) may be single-stranded or double-stranded may be circular or linear may be in one piece or in multiple segments The genome is much smaller than a cell’s genome. DNA directs the host cell to make new virus copies. Uses the same genetic code as all living organisms RNA may be directly transcribed, or replicated first. RNA viruses use enzymes that make more errors RNA viruses mutate more frequently Viral Classification Challenges Most viruses evolved from different ancestors Viruses have no common genomic sequence Ways to classify Capsid structure Enveloped/ non-enveloped Genomic structure Steps of a Virus Lifecycle A virus must use the host-cell processes to replicate. 1. Attachment 2. Entry 3. Replication 4. Assembly 5. Release/ egress 1. Attachment Receptors on the surface of the host cell bind to virus capsid proteins or virus envelope glycoproteins. Viruses can attach only to cells that have the right receptor molecules. ○ Species and cell type specific A virus and its host receptor protein. The HIV virus binds the CD4 receptor on the surface of human cells. CD4 receptors help white blood cells to communicate with other cells of the immune system when producing an immune response. 2. Entry 1. Injection of genome – bacteriophage 2. Fusion with membrane 3. Endocytosis Bacteriophages attached to a host cell (transmission electron micrograph). In bacteriophage with tails, like the one shown here, the tails serve as a passageway for transmission of the phage genome. 3. Replication Transcription or translation of the viral genome Synthesis of viral proteins and genome by the host cell 4. Assembly Viral proteins are packaged with the newly replicated genome into new virions to be released from the host cell 5. Egress Virus release via Lysis: results in host cell death Budding: enveloped viruses do not usually kill host cell Exocytosis: use host cell exit pathways Influenza Virus Infection Bacteriophages Infect only bacteria Capsid can be any shape, but head-tail is unique to phages Lytic cycle: phage infects a bacterium, uses bacterium for viral replication, lysis occurs Lysogenic cycle: phage infects a bacterium and inserts its DNA into the bacterial chromosome, phage DNA is now copied and passed on to each successive generation Viral reproduction without host cell death Some phages reproduce only via lytic lifecycle, others alternate between lytic and lysogenic Bacteriophage Lifecycles Bacteriophage T4 Infects the bacterium, Escherichia coli Has a DNA genome Has been studied extensively Plant Viruses Viruses cannot cross cell wall = most require a vector or damaged tissue Horizontal transmission: between same species but not parentoffspring virus typically enters by way of damaged plant tissue may come from infected sap or vectors such as insect bites or nematodes Vertical transmission: parent to offspring virus is transmitted from the parent plant to the seeds May cause hypoplasia or hyperplasia May cause necrosis of the plant or plant tissue Animal Viruses May cause: Acute disease (colds, influenza) Chronic infection (hepatitis C) Latency and intermittent symptoms (herpes simplex) remains in nerve tissue for life reactivation causes active replication and cell lysis Asymptomatic infection (other human herpes viruses) Oncogenesis (hepatitis C, human papillomavirus [HPV]) Animal Viruses HIV Retrovirus Causes AIDS (acquired immunodeficiency syndrome) Is enveloped Has enzymes and proteins Retrovirus: uses reverse transcriptase to convert its RNA genome into DNA to insert into host cell ○ Normally, DNA transcribed to RNA Varicella-Zoster – chicken pox virus Childhood chicken pox infection → viral latency → possible reactivation later in life as shingles (a) Varicella-zoster, the virus that causes chickenpox, has an enveloped icosahedral capsid visible in this transmission electron micrograph. Its double-stranded DNA genome becomes incorporated in the host DNA and can reactivate after latency in the form of (b) shingles, often exhibiting a rash. HPV HPV, or humans papillomavirus, has a naked icosahedral capsid visible in this transmission electron micrograph and a double-stranded DNA genome that is incorporated into the host DNA. The virus, which is sexually transmitted, is oncogenic and can lead to cervical cancer. Vaccines prevent viral infections Trigger immune response Prepared using: Attenuated “live” virus* Very small risk of infection Possibility of back mutations “Killed” virus Molecular subunits Antiviral Drugs Difficult to block the activities of a virus without damaging a host cell Inhibit the virus by blocking the actions of its proteins Tamiflu works by inhibiting an enzyme that allows new virions to leave their infected cells → inhibits spread of the virus Anti-HIV drugs inhibit replication at several different phases of the life cycle to combat the virus’ high mutation rate – HAART: highly active antiretroviral therapy Fusion inhibitors Reverse transcriptase inhibitors Integrase inhibitors Protease inhibitors Fusion inhibitors Protease inhibitors Reverse transcriptase inhibitors Integrase inhibitors Prions Smaller than viruses; made of proteins; infectious particles Contain no nucleic acid Cause fatal neurodegenerative diseases Mad cow disease (BSE, bovine spongiform encephalopathy) Creutzfeldt-Jakob disease (in humans) Kuru (in humans, spread by cannibalism) Scrapie (in sheep) Chronic wasting disease (in deer, moose, elk) Prions are not destroyed by cooking. Viroids Small circles of RNA Lack capsid and envelope Use host cell for reproduction like viruses Do not make proteins Only known to infect plants These potatoes have been infected by the potato spindle tuber viroid (PSTV), which is typically spread when infected knives are used to cut healthy potatoes, which are then planted. The Origins of Life on Earth Conditions on Early Earth Almost no atmosphere: volcanic gases such as hydrogen sulfide, methane, and carbon dioxide Intense solar radiation Strong volcanic activity Constant bombardment by meteorites and comets History of Earth Earth is ~4.5 byo Scientists think Earth developed conditions for life ~4.3 bya Break in the asteroid bombardment Cooler temps allowed condensation to form oceans Second round of bombardment ~3.9 bya Oldest fossils are ~3.5 byo Sulfur-metabolizing bacteria Life may have evolved multiple times during the billion year gap The mystery of the origins of life To account for the origin of life on our Earth requires solving several problems: 1. How did the organic molecules that define life (amino acids, nucleotides) originate? 2. How were macromolecules assembled (proteins, nucleic acids) - a process requiring catalysts? 3. How were macromolecules able to reproduce themselves? 4. How were these macromolecules assembled into a system separate from their surroundings (i.e., a cell)? Hypotheses on the origin of organic compounds Hypothesis 1: Organic molecules were synthesized from inorganic compounds in the atmosphere, Hypothesis 2: Organic molecules rained down on the Earth from outer space, Hypothesis 3: Organic molecules were synthesized at hydrothermal vents on the ocean floor, and/or Hypothesis 4: Organic molecules were synthesized when comets or asteroids struck the early Earth. H1: Oparin-Haldane Hypothesis – 1920s Life arose from inorganic molecules: gradual chemical evolution Primordial soup: inorganic molecules + energy = building blocks such as amino acids and nucleotides Oxygen-poor atmosphere Building blocks combined to form larger, more complex molecules Polymers assembled into structures capable of sustaining and replicating themselves Details probably not correct, but overall model might be H1: Miller-Urey Experiment – 1950s Atmospheric synthesis Tested the Oparin-Haldane hypothesis Recreated environmental conditions of early Earth H2O, NH3, CH4, H2 Energy source: electricity to simulate lightening Produced organic molecules such as amino acids, sugars, and lipids Probably not an accurate simulation of ancient Earth, but other studies have shown that organic building blocks can be formed from inorganic molecules H2: Exogenous Delivery Organic molecules seeded by comets, meteorites, space dust Evidence: Meteorite in Australia in 1969 contained dozens of different amino acids 3.3 billion year old extraterrestrial organic matter found in sediment in S. Africa Material collected from the surface of an asteroid H3: Synthesis at Deep-Sea Hydrothermal Vents Energy source: chemical gradient High amounts of hydrogen, hydrogen sulfide, carbon dioxide, iron, sulfur Vent microbes are some of the most primitive living organisms (Archaea) Deep ocean was protected from meteorite bombardment and lethal radiation H4: Synthesis by Destruction Energy source: impact from meteorites Inorganic molecules in the presence of clay can be converted to organic molecules Problem 2: Macromolecule Assembly Monomers → polymers Enzymes are responsible for assembly in cells today Enzymes are a polymer → chicken-and-egg problem Mineral surfaces such as clay act as catalysts Template for formation of polymers Release of electrons to provide energy to form chemical bonds Act as catalysts to speed reactions Polypeptides and polynucleotides (RNA molecules) have been linked together on clay surfaces Problem 3: Reproduction of Macromolecules Identical copies of macromolecules in order to keep continuity of life from one generation to the next RNA stores information, but some RNA can also act as a catalyst for chemical reactions: ribozymes RNA World hypothesis: A single macromolecule could be both the genetic carrier and the catalyst to copy itself Natural selection: best replicators would produce greater numbers in each succeeding generation Problem 4: System Assembly Machinery of life must be separate from its surroundings so the building blocks are held in higher concentration to facilitate chemical reactions Research has shown that fatty acids and other molecules synthesized under prebiotic conditions can form lipid bilayers and spontaneously assemble into enclosed vesicles; supports primordial soup hypothesis Development of Life on Earth Pathway to a cell: 1. Precursor chemicals 2. Formation of small organic molecules 3. Organic molecules form polymers 4. Genetic material encodes proteins 5. Lipids form spheres