* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Document
Non-coding DNA wikipedia , lookup
Synthetic biology wikipedia , lookup
Protein (nutrient) wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Bottromycin wikipedia , lookup
Transcriptional regulation wikipedia , lookup
Western blot wikipedia , lookup
Messenger RNA wikipedia , lookup
Silencer (genetics) wikipedia , lookup
Non-coding RNA wikipedia , lookup
Protein adsorption wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Molecular evolution wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Point mutation wikipedia , lookup
Protein structure prediction wikipedia , lookup
Cell-penetrating peptide wikipedia , lookup
Epitranscriptome wikipedia , lookup
Gene expression wikipedia , lookup
Expanded genetic code wikipedia , lookup
Genetic code wikipedia , lookup
Deoxyribozyme wikipedia , lookup
List of types of proteins wikipedia , lookup
Lecture Outline Molecular biology - the chemical basis of terrestrial life Cellular biology - “life as we know it” The origin of life on Earth Implications for astrobiology Carbon (C) is a unique element, key role in organic chemistry and molecular biology Strong C-C bonds provide the structural support for very large 3D molecules C can simultaneously form strong bonds with H and O thus allowing large and complex molecules CO2 is a gas allowing easy C transport and interactions Organic (C structured) compounds are 50x more numerous than inorganic ones Not particularly abundant in the Earth’s mantle, [C/O]Mantle=10-3[C/O]Cosmic (carbon starvation?) Liquid Water: Essential for Life Essential for terrestrial biology Water is a flexible solvent Lots of local order in water Cells are mostly water Water is an excellent solvent Likes Water OH COO Sugars Polar solvents Doesn’t like water CH3 CH2-CH2- Four major classes of bio-molecules Proteins: chains of amino acids that are the functional “machines” of biology Nucleic Acids: lengthy sequences of nucleotides which store, copy & implement protein structures Carbohydrates: energy storage & structure Lipids: energy storage & cell membranes All 4 types of bio-molecules are long polymers made of a set of identical “building blocks” The ® Lego Principle • Biology is largely built from on a small number of components: - 20 L amino acids - 5 nucleotide bases - a few D sugars & fatty acids • A common property of biology (and mass-produced children’s toys) throughout the universe?? Nucleic Acids: Three key self-propagation mechanisms DNA (info archive)storage and replication DNA to RNA (blueprint) transcription RNA to protein (hardware) construction RNA only ?? (RNA World Hypothesis) The functioning of these mechanisms requires a genetic code/language, a bio-energy supply and carrier (ATP, Adenosine Triphosphate), a “building tool” (ribosome) and water as a medium. All above are universal features of terrestrial life! Amino acids are the “lego” building block components of proteins 13 to 27 atoms of C, O, N, H & S A COOH (carboxy) end that “loses” a H+ ion A NH2 (amino) end that “takes” a H+ ion More than 170 known, but only 20 are coded by nucleic acids and “used” to make proteins 19 are l-chiral (left-handed) & one is symmetric Carboxy & amino ends “plug” together to form a peptide bond and thus make long chains: H3N+ + COO- -> OC-NH + H2O Amino Acids The 4 levels of protein structure Peptide bond chains of 100s of amino acids Chain winds to form an -helix or folds to form a -sheet stabilized by H bonds Fold into specific 3D shapes set by disulfide bonds and hydrophobic interactions Also such proteins may combine as subunits to form a larger and more complex protein Protein Structure Protein functions = many and diverse Structure Enzymes Hormones Transportation Protection Sensors Toxins Gates Movement Proteins comprise >50% of the mass of many cells (the rest being largely water). More than 104 human proteins are known. Genetic information specifies proteins and nothing else. Nucleic acids (DNA and RNA) Very long chains (again) of nucleotides Each nucleotide is made of a phosphoric acid, a sugar and a base Sugar is d-ribose in RNA & deoxy-dribose in DNA RNA bases are Cytosine, Uracil, Adenine & Guanine; DNA bases = C, A, G & Thymine DNA structure & replication Consists of two nucleotide chains/strands wrapped around each other in a spiral helix A on one strand matches T on the other Similarly G and C pair between strands When the strands are separated, they can each regenerate their partner & thus copy the information they encode A codon consists of 3 sequential bases and specifies one amino acid (or start/stop) DNA Nucleotides RNA structure & transcription Consists of a single chain/strand of nucleotides Organized in the same 3 base codons as DNA except that U replaces T DNA generates/transcribes messengerRNA (mRNA) which provides the “working blueprint” for protein synthesis Protein synthesis/construction mRNA carries the amino acid sequence information for the protein transfer-RNA (tRNA) provides the raw material amino acids by binding them to anti-codon (complementary base triplets) Ribosome macromolecule/protein reads mRNA to select specified amino acids from tRNA and extrudes them in a chain as it moves along the mRNA ATP energizes the individual bondings by transfer of a phosphate group to a X-OH component mRNA, tRNA & ribosome are reusable for additional syntheses, but ATP degrades to ADP & must be reenergized What is Life? Definition of Life (many possibilities) Metabolism (chemical activity) Growth/development Energy utilization Local entropy reduction Preservation of information/identity Procreation Mutation Spatial boundaries Functional in abiotic environments Cells Cells are alive, satisfy all definitions of life All “normal” life forms are cellular Most terrestrial life is unicellular Cells are enclosed by a membrane Within cells the processes of molecular biology occur in an aqueous solution Cells organize/utilize a large number of biomolecules & their interactions -> life Two fundamental classes of cells Prokaryotes: no nucleus & relatively little internal structure Eukaryotes: nucleus containing cell’s DNA, defined by an inner membrane, & complex internal structures Quite different in many ways Major clue to the evolution of life on Earth Properties of prokaryotes No nuclear membrane Single circular strand of DNA mRNA generated from start to stop codons No internal organelles & little structure Relatively small (0.1-10m diameters) Ancient,oldest life forms (3.9 Gyr ago ?) Two evolutionary branches (split 3.5 Gyr ?) Archaea “Third kingdom” Archaea differ more from bacteria than we do from bacteria Structurally like bacteria; however, archaea have metabolic pathways similar to eukaryctes Use a wide variety of energy sources including ammonia, metal ions, free hydrogen Many extremophiles are archaea No pathogens or parasites! Methanogens in our guts http://www.ucmp.berkeley.edu/ archaea/archaea.html Two typical prokaryotes Properties of eukaryotes DNA segregated into nucleus by membrane Multiple linear stands of DNA An intermediary mRNA is “edited” into exon and intron segments -> final mRNA Complex internal structure/many organelles Relatively large (10-100m diameters) Relatively recent (appeared 2-3 Gyr ago) Unicellular and all multi-cellular life forms Exon/intron editing during transcription Typical eukaryote internal structures Major eukaryote organelles Nucleus Cytoskeleton Flagellum Lysosome Mitochondrium* Peroxysome Endoplasmic reticulum Golgi apparatus Plastids DNA, DNA->mRNA Internal transport/support Movement Digestion/waste removal Food+oxygen -> ATP Fat metabolism Protein & lipid synthesis Protein & lipid storage photosynthesis Origin of biochemistry First produce the macromolecule building blocks Happened very fast, 4 Gyr ago (Earth just cooled) Possible locations/environment Shallow tidal pools or lagoons (Darwin) Deep sea hydrothermal vents On wet clay surfaces Deep underground? Proteins or nucleic acids first?? (chicken & egg issue) RNA biology first (no DNA or proteins)? RNA world? Oparin-Haldane Hypothesis Urey-Miller Experiment (1953) water (H2O) methane (CH4) ammonia (NH3) hydrogen (H2) no oxygen + sparks YIELDS amino acids! (>2% of C in one week) Urey-Miller experiment issues & subsequent developments Seminal influence on origin of life studies Many variations on details work also All DNA/RNA bases later produced in (HCN) experiments No progress in assembling building blocks into “useful” macromolecules by similar techniques Now believed that Earth’s primordial atmosphere was CO2 dominated & had little CH4 which very much reduces the amino acid yields U-M conditions resemble oceanic hydrothermal vents Clay surfaces may facilitate macromolecule assembly Origin of cellular life Also very very fast (3.7 - 3.9 Gyr) Requires formation of enclosing lipid membranes Simple protein membranes have been formed spontaneously in lab experiments Membranes need to effectively isolate important macromolecules & their reactions but not seal off environment completely (complex function) Speculative possibility of noncellular ancestors?? Prokaryote microfossil dated at 3.7 Gyr Mitochondria and Lysosomes *Mitochondria have their own internal DNA (loop) and reproduce separately from the cell! Note internal complexity of these organelles, likely endosymbionts. General Characteristics of the Molecular Biology of Terrestrial Life Extraordinarily complex & inter-connected chemical processes, vastly richer than any other known chemical systems Basic biochemistry shared by all known terrestrial organisms as well as many of its details Carbon based and water dependent Hierarchically structured (using much simpler subcomponents), polymerized macromolecules Few (4) general classes of compounds but many individual ones with highly specialized and specific biological functions Implications for Extraterrestrial Life Requires no exotic conditions or constituents Appears to have happened only once on Earth Intricate complexity -> origin problem No obvious route of gradual development Jump in complexity wrt other natural chemistry Absence of theoretical or empirical alternative biochemistries -> one type of life only?? Physical mechanism for evolutionary adaptation and development once started Evolution of cellular life Last Common Ancestor = prokaryote, anaerobic heterotrophe, maybe ≤ 250 genes, resembling present day mycoplasmas (<500 genes) Even simpler RNA-only cells a possibility? Split into Archaea and Bacteria classes (3.5 Gyr ?) Anaerobic autotrophs/chemoautrophs next Photoautotrophs, cyanobacteria (2.7 - 2.5 Gyr) O2 respiration by 2.2 Gyr (high octane biology!) Eukaryotes w ~6000 genes, evolved via endosymbiont “colonization”? (3 - 2 Gyr) Multicellular life consisting of eukaryotes (1 Gyr) Implications for extraterrestrial life Multiple hurdles: Biochemistry (proteins & nucleic acids) Cells Autotrophism (chemo/photo-synthesis, food) Internal organelles Oxygen respiration Multicellular cooperation Appearance time is often interpreted to imply probability/improbability of each development Convergence or Divergence of Cosmic and Biological Evolution? (How similar to here?) Large/coarse scales -> convergence But on some small/fine scales -> divergence Divergence might begin on the scale of planetary systems since known extrasolar systems are unlike the Solar System However it might not occur until far finer levels of detail <- assumption!