Lecture Outline

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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

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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 Earths mantle,
  C/OMantle10-3C/OCosmic (carbon starvation?)

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Liquid Water Essential for Life

• Essential for terrestrial biology
• Water is a flexible solvent
• Lots of local order in water
• Cells are mostly water

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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

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All 4 types of bio-molecules are long polymers
made of a set of identical building blocks
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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
  childrens toys) throughout the universe??

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Nucleic AcidsThree 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!
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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- -gt OC-NH H2O

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Amino Acids
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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

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ProteinStructure
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Protein functions many and diverse

• Structure
• Enzymes
• Hormones
• Transportation
• Protection
• Sensors
• Toxins
• Gates
• Movement

• Proteins comprise gt50 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.

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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-d-ribose in DNA
• RNA bases are Cytosine, Uracil, Adenine
  Guanine DNA bases C, A, G Thymine

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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)

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DNA Nucleotides
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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 messenger-RNA (mRNA)
  which provides the working blueprint for
  protein synthesis

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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
  re-energized

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What is Life?
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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

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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 -gt life

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Two fundamental classes of cells

• Prokaryotes no nucleus relatively little
  internal structure
• Eukaryotes nucleus containing cells DNA,
  defined by an inner membrane, complex internal
  structures
• Quite different in many ways
• Major clue to the evolution of life on Earth

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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 (0.1-10?m diameters)
• Ancient,oldest life forms (3.9 Gyr ago ?)
• Two evolutionary branches (split 3.5 Gyr ?)

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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
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Two typical prokaryotes
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Properties of eukaryotes

• DNA segregated into nucleus by membrane
• Multiple linear stands of DNA
• An intermediary mRNA is edited into exon and
  intron segments -gt final mRNA
• Complex internal structure/many organelles
• Relatively large (10-100?m diameters)
• Relatively recent (appeared 2-3 Gyr ago)
• Unicellular and all multi-cellular life forms

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Exon/intron editing during transcription
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Typical eukaryote internal structures
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Major eukaryote organelles

• Nucleus
• Cytoskeleton
• Flagellum
• Lysosome
• Mitochondrium
• Peroxysome
• Endoplasmic reticulum
• Golgi apparatus
• Plastids

• DNA, DNA-gtmRNA
• Internal transport/support
• Movement
• Digestion/waste removal
• Foodoxygen -gt ATP
• Fat metabolism
• Protein lipid synthesis
• Protein lipid storage
• photosynthesis

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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?

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Oparin-Haldane HypothesisUrey-Miller Experiment
(1953)

• water (H2O)
• methane (CH4)
• ammonia (NH3)
• hydrogen (H2)
• no oxygen
• sparks
• YIELDS
• amino acids! (gt2 of C in one week)

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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 Earths 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

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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??

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Prokaryote microfossil dated at 3.7 Gyr
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Mitochondria and Lysosomes
Mitochondria have their own internal DNA (loop)
and reproduce separately from the cell!
Note internal complexity of these organelles,
likely endosymbionts.
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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

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Implications for Extraterrestrial Life

• Requires no exotic conditions or constituents
• Appears to have happened only once on Earth
• Intricate complexity -gt origin problem
• No obvious route of gradual development
• Jump in complexity wrt other natural chemistry
• Absence of theoretical or empirical alternative
  biochemistries -gt one type of life only??
• Physical mechanism for evolutionary adaptation
  and development once started

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Evolution of cellular life

• Last Common Ancestor prokaryote, anaerobic
  heterotrophe, maybe 250 genes, resembling
  present day mycoplasmas (lt500 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)

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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

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Convergence or Divergence of Cosmic and
Biological Evolution? (How similar to here?)

• Large/coarse scales -gt convergence
• But on some small/fine scales -gt 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 lt- assumption!

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