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Everyday Biology th Day 3 (April 5 ) Everyday Chemistry Emergence • Complicated behaviors and patterns can often emerge from simple underlying rules • Separation, alignment, cohesion • Life as an emergent property -­‐ a collection (not one or two) of specific non-­‐living things -­‐Life has certain features • Complicated behaviors and patterns can often emerge from simple underlying rules • Biological systems: cells -­‐ brain -­‐ behavior • At the molecular level -­‐ polymers -­‐ Behavior of molecules based on the rules of chemistry Polymerization is central to biology -­‐Harnessing chemistry to efficiently “evolve” -­‐Covelant and Hydrogen Bonds -­‐Polymerization: individual molecules assemble into long chains • harnessing chemistry to efficiently “evolve” • Nucleotides à DNA, RNA 4 monomer types • Monomer +Monomer à Polymer • Amino acids à polypeptide/protein 20 monomer types A few types of monomers generate a tremendous diversity of polymers. Building Blocks of “life” The Atoms and Molecules of Life All life forms on earth are carbon-­‐ based (organic) -­‐ the "backbone" of biology • Carbon forms the backbone of most key molecules of life • Water (H2O) accounts for most of the Oxygen 2 Why Carbon • Two qualities of carbon: small size (radius) and unique electron configuration (molecular glue) • Molecular glue: valence of 4 – can make up to four bonds -­‐H, O, N, S AND itself, C, to make “carbon backbon es’ • Small size: carbon radius small 3 Chemistry of Life: Atoms Electronegativity -­‐attract electrons Number of valence electrons i t A -­‐Carbon is small -­‐Carbon like to make 4 bonds -­‐Valence electrons are the glue that can hold molecules together =reactivity. Atoms prefer to have the valence or outer shell comprised of 8 electrons. Levels of Organization Atoms à Molocules Polymerization (carbon Mol) How are molecules formed and how do they interact • Covalent bonds: hold atoms together within molecules -­‐ sharing of electrons -­‐ very strong glue 4 • Ionic: donating/accepting electrons to become an ion, easily formed between valence 1 and 7 atoms such as Na+ Cl-­‐ • Hydrogen bonds -­‐ where hydrogen forms bonds simultaneously with two other atoms. -­‐Facilitates interaction between molecules with unlike atoms which have partial charges due to their respective differences in electronegativity. Why Water • The best solvent -­‐ it dissolves things really well • Large liquid range • It has capillary action -­‐ adhesive • High heat capacity: absorbs heat -­‐it protects us • Water can form an acid and a base -­‐involved in acid/base chemistry in life Drives the formation of larger structures essential for life: proteins and lipid membranes The Essential Water -­‐Charge distribution of water • The electronegative oxygen atom pulls electron density away from hydrogen. • The oxygen carries a partial negative and the hydrogen atoms carry partial positive charges. -­‐Water has a permanent dipole -­‐ water is “polar” 5 Liquid water • Each water molecule is held within a dynamic framework of 0 -­‐4 hydrogen bonds depending on the location of water i.e., air interface. • The mutual attraction between water molecules is called "cohesion." Polar Vs. NonPolar and Water Solubility Polar • Water is polar • Oxygen tends to create polar molecules • Sugars are polar and water soluble or hydrophilic Nonpolar • Methane is nonpolar • Carbon and hydrogen tend to create nonpolar molecules • Grease is nonpolar and not water soluble or hydrophobic The Hydrophobic Effect • The observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules. • Non polar substances disrupt hydrogen bonds B/T water • Charles Tanford “The Hydrophobic Effect: Formation of Micelles and Biological Membranes” Science 1978 • The hydrophobic effect drives self-­‐ organization of membranes and protein folding -­‐ proteins have evolved to contain hydrophobic “cores”. 6 Higher Order Life Molecules • DNA -­‐Phosphates Links -­‐Base gives Identity -­‐Cellulose (sugar) Backbone • Protein -­‐Amino groups -­‐Amino Acids joined by peptide group -­‐Peptide bonded backbone A few types of monomers generate a tremendous diversity of polymers -­‐There are more than 10^10 different possible DNA sequences of length 17. -­‐DNA Polymerase copies each strand of DNA double helix Biological Membranes Atoms à Molocules à Polymerization (lipids) • Membranes: Impearable to water and boundaries that define compartments • Membranes separate the inside of a cell from the outside • Membranes define specialized compartments within a cell 7 The RNA hypothesis: • RNA as the original spontaneous polymer that could replicate chemically • fatty acids which could assemble to create a compartment that can grow and divide and facilitate RNA replication • Current DNA-­‐RNA-­‐protein-­‐lipid-­‐based life evolved from self replicating RNA molecule or RNA-­‐like molecule plus lipid based system. • RNA can store information (like DNA) AND catalyze (like protein) all of the chemical reactions required for life. • RNA is needed to make proteins (ribosome) and catalyzes peptide bond formation. • Many essential cofactors in cell (ATP, NADH, acetyl -­‐CoA) are structurally related to RNA • Deoxyribonucleotides (DNA) are made from ribonucleotides, which makes RNA. Microbes • Bacteria • Archaea • Eukaryotes -­‐Some earliest evidence of life are microfossils interpreted to be bacteria based primarily on size/shape -­‐Relationships among species are deduced from shared characteristics, including sequences of DNA 8 Common ancestry around 1843 • Common ancestor gives rise to 2 independent lineages • Natural groups, or “clades”, share certain properties (one invention) • Pattern of change (tree topology or pattern) • Rate of change (branch length) • Length of line proportional to amount of change (varia ble) • Phylogenetic trees are representations of evolutionary relationships Homology “The same organ in different animals under a variety of form and function” ’ • Because all life shares a common ancestry -­‐ so should the “parts” of life • Homology is similarity due to common descent • Analogy is due to adaptation to the same environmental condition (convergence) • “Levels” of homology’ Steps in Assessing Homology 1. Classify features 2. Classify similar in similar positions (e.g.structures) 3. Link features to tree of evolutionary relationships 9 Relationships among species are deduced from shared characteristics, including sequences of DNA Heredity -­‐ genetics -­‐ genes (the code) End of Notes Day 3 10 Day 4 (April 7 ) Origin of life-­‐ Viral Life Diversity in microbes • is reflected in the way that they: -­‐ obtain energy and nutrients -­‐ respond to environment -­‐ regulate genes -­‐ survive adverse conditions ... not as in shape (morphology) “natural” groups of organisms (or genes) Branches can rotate around nodes Nodes are can rotate 360° -­‐ like a mobile 11 Microbes • Carl Woese used rRNA genes to determine “natural” or evolutionary relationships among microbes Requirements of a gene “proxy” for an organismal phylogeny • The Ribosome (70S-­‐80S) • Ribosomes are present in all cellular life • Homologous: similar in position, structure, and evolutionary origin but not necessarily in function. • ribosomes are the cell’s protein factory and are composed of proteins and RNA • ribosomal RNA (rRNA) = RNA component of the ribosome • some regions of rRNA is variable and some regions are not as variable Multiple sequence alignment: • taxa in rows • homologous positions in columns • use “gaps” or “indels” to bring homologous • positions in alignment 12 The “Big Tree” • All cellular life is related (one origin) • Last universal common ancestor (LUCA) • Three domains of life, not two: Bacteria, Archaea, Eukarya • Most life is microbial (still) • Natural taxonomy: based on evolutionary relatedness i.e, allows phylogeny to be predictive à Related organisms (or related genes) should have similar properties (not that we always know “which” properties those are) • How do you get bigger Energy canyon.... • Archaea + bacteria overcome the “energy” canyon Two groups of bacteria are related to eukaryotic organelles (mitochondria and chloroplast) 13 Domain of Life (1977) • Kuhnian paradigm shift (scientific revolution) • Lack of understanding of archaeal biology • Much research was on Archaea in Germany • Genomes and new microbes have helped Ongoing “prokaryote” debate Risk • Risk is the likelihood of X happening Calculating Risk • Relative Risk: is the ratio of the probability of an event occurring (for example, developing a disease, being injured) in an exposed group to the probability of the event occurring in a comparison, non -­‐exposed group. • Increased Risk: Probability that the risk of a given situation will go up. Example of Calculating Risk • 24 Ebola infections/2014 • 33 people/year die by lightening Fraction: 24 people/year out how many 316,000,000 • 1/13.1 million people Frequency of X: 7.6 x 10-­‐8 • 7.6 x 10-­‐8 x 100 = 0.0000076% 14 Calculating Risk Discovery Of Viruses • 1880s Tobacco Mosaic Virus (Beijerinck/Ivanovski) • He took sap of sick plants and injected into healthy ones • It grew bacteria from sap -­‐ not infectious • He then added it to contagious fluid: • He used alcohol and boiled it • let it dry on paper • still infectious Martinus Beijerinck • Filtered sap from sick tobacco plants took juice and then infected tobacco -fluid caused disease = contagious living fluid = virus 15 Later Discoveries à 95% protein but also DNA and maybe sometimes RNA à protein shells holding a just few genes Relative Size of Viruses General Characteristics of Viruses • Need cells to replicate • Contain a single type of nucleic acid, • Either DNA or RNA (not both) • Single-­‐ or double-­‐stranded • Contain a protein coat that surrounds the nucleic acid Some are enclosed by an envelope • Some viruses have spikes • Viruses infect all forms of cellular life: But viruses infect specific types of cells in one host 16 Viral Structures • Nucleic acid -­‐DNA or RNA (>2 genes < ) Capsid • Capsomeres (units of capsid) • Envelope: made of lipids obtained from the host Spikes • Virion: a complete infectious particle • Nucleocapsid: nucleic acid plus capsid Are Viruses Alive • Viruses have genetic material (DNA, RNA, protein) • They can replicate (but require a host) • They exchange genetic information with living things don’t make their own energy • “borrowed” life emergent property of non-­‐living things • Radiolab: Shrink (Mimivirus) • They self Assemble Flu (influenza) • every year 5-­‐10% of adults and 20-­‐30% of children get the flu 250,000-­‐ 500,000 die of flu every year • infects lining of airways and paves ways for other infections flu comes from birds (also hosts) • flu virus can mutate, then adapt to human hosts • sometimes cells have > 1 kind of virus, and viruses can combine and swap genes 17 BIOSYNTHESIS: RNA Viruses • Host cells do not possess RNA-­‐dependent polymerases. • These enzymes are required to make viral mRNA and replicate genomes. • Viruses do have RNA-­‐dependent polymerases • RNA viruses are classified using a (+) or (–) strand designation for their genomes • Double-­‐stranded RNA viruses contain one (+) strand and one (–) strand. Single-­‐stranded RNA viruses are either: -­‐(+) single-­‐stranded -­‐(–) single-­‐stranded Why do viruses have specificity for certain cells • Viruses enter cells after binding to highly specific cell surface proteins • Viruses must be able to replicate in their host cells and escape from them Why can some viruses infect multiple hosts • Viruses enter cells after binding to highly specific cell surface protiens • Other species have homologs of these key proteins 18 BIOSYNTHESIS: Double-­‐stranded DNA Viruses • Double-­‐stranded DNA viruses use the same mechanisms as the host cell for biosynthesis. • One strand of viral DNA is transcribed into mRNA. It uses either the host cell or viral RNA polymerase. • How does a virus cause cancer • Viruses need to use the host cell machinery to replicate. • This extra activity can cause increased cell division • HPV can boost the activity of the host cell’s machinery that copies DNA. • Increased cell division combined with additional mutations leads to cancer BIOSYNTHESIS: (+) Single-­‐stranded RNA Viruses • The (+) strand is already mRNA. -­‐It can be directly translated into viral proteins. • Genome replication has 2 steps: • The (+) strand is copied into (–) template • The template is used to make more (+) strands. 19 Why do we have “receptors” for viruses • HIV uses cell surface proteins called • CD4 and CCR5 as “receptors” • People with mutations in CCR5 are resistant to HIV • CCR5 has a “normal” function. It detects chemical signals to help recruit immune cells to sites of infection • CD4 and CCR5 are present on the surface of certain immune cells • HIV has co-­‐opted this protein to be a virus receptor Why do we have “receptors” for viruses • HIV uses cell surface proteins called CD4 and CCR5 as “receptors” • People with mutations in CCR5 are resistant to HIV • CCR5 has a “normal” function. It detects chemical signals to help recruit immune cells to sites of infection • CD4 and CCR5 are present on the surface of certain immune cells • HIV has co-­‐opted this protein to be a virus receptor Viruses Mediate Evolution • Endogenous Retroviruses • retroviruses -­‐ insert genetic material into host DNA • "endogenous” = from within riddled with copying mistakes 20 • remain a silent, hobbled passenger in the genome • viral genomes become part of host genome many remain dormant and are not pathogenic We are actually part virus: • the human genome about 100,000 copies of dead viruses in our genome = 8% of our total DNA • one virus carries a protein called syncytin expressed in the placenta • in all placental mammals, syncytin is key for drawing nutrients into the embryo’s bloodstream Giant Viruses • First discovered in 1999 as pathogens of algae They often infect amoeba • Size of particles can be ~200 nm (violates the size paradigm) • Family: nucleocytoplasmic large DNA virus (NCLDV) Genomes can be as big as those of some bacteria • They can even be parasitized by other viruses (e.g. the virophage Sputnik) • Mimivirus was originally mistaken for a bacterium, because of its size and it was identified during investigation of a pneumonia outbreak associated with a water cooling tower in the U.K. 21 Where did this giant virus come from • Originate from simple virus -­‐ acquire genes from hosts. • But, very few genes have homology to host genes (<10%) • Reductive evolution: a cellular form of life reduced its essential genes -­‐ parasite • But, no obvious homology with any of the major domains of life. • Pre-­‐date cellular life -­‐ some gave rise to cells others stayed as giant virus End of Notes Day 4 Week 2 22