CMSC 828N Introduction: Molecular biology background

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CMSC 828N Introduction Molecular biology
background
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Class web page

• http//cbcb.umd.edu/confcour/CMSC828N.shtml

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Course grading

• 3 laboratory assignments
• 15 (Labs 1,2,3)
• Lab 1 given out by Sept 9, due Sept 23 (see
  syllabus)
• Labs due by midnight on due date
• Late penalty 10/day for 2 days maximum
• 1 class presentation of a research paper
• 5
• Lab 4 (mini-project)
• 25
• Final exam
• 25

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UMD Plagiarism policy

• Does this really happen?
• Yes
• Acknowledgement many of the slides that follow
  are from Michael Brent, a professor at Washington
  Univ.
• What if I have a question?
• You are required to ask if
• you have any doubt about whether or not you can
  use any (text,code,data) as part of your work for
  this class

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Life

• Categories
• Cellular organisms, viruses, prions
• Cells are surrounded by a membrane
• By weight, inside is mostly water
• Generally, outside is aqueous, also
• Major categories of cellular organisms are
• Prokaryotes
• Eukaryotes

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Prokaryotes

• Single-celled organisms
• Only 1 membrane. I.e., single compartment
• Typically about 1 micron diameter

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Prokaryotes
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Eukaryotes

• Single-celled organisms, plants animals
• Typical cell is 10 microns across (variable)
• Membrane-bound nucleus contains DNA

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Eukaryotes
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Some other clades
Tree of life animals
Entrez taxonomy
Entrez taxonomy
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Cell contents small molecules

• Examples
• Ions (Ca, K, Na, Cl-)
• Sugars
• Fats
• Vitamins
• Can be obtained by
• Import through membrane
• Synthesis from imported precursors
• Synthesis de novo

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Macromolecules (polymers)

• Synthesis
• Made in cell by linking monomers from a specified
  set
• Examples
• Polysaccharides (sugar chains)
• Proteins (amino acid chains)
• DNA RNA (Nucleic acids nucleotide chains)

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Protein functions

• Structural e.g.,
• Cytoskeleton gives membrane strength rigidity
• Signaling (information transduction)
• receptors on cell surface sense hormones
• DNA binding to turn genes on and off
• Enzymatic speed up reactions to, e.g.,
• Extract energy from nutrients
• Interconvert small molecules
• Immune response bind and degrade invaders
• Maintain circadian rhythm other clocks

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Protein functions

• Enzymatic functions (cont.)
• Programmed cell death (apoptosis)
• Build macromolecular chains
• Copy cells DNA during replication
• Build other proteins from DNA instructions
• Active transport through membrane
• E.g. specific sugar transporters
• Etc., etc., etc.
• Web resources
• GO Browser, KEGG pathways, BioCarta pathways

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Proteins

• Built from 20 monomers called amino acids
• Spontaneously fold into conformations determined
  by their amino acid sequences
• Folded shape is essential to function
• Often associate into complexes

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Nucleic acids

• Two major types of nucleic acid polymers
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA).
• Composition
• Four monomers called nucleotides
• DNA deoxy
• Adenine (A), Guanine (G), Cytosine (C), Thymine
  (T)
• RNA
• Adenine (A), Guanine (G), Cytosine (C), Uracil (U)

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DNA

• Function
• Long term information storage transmission
• Structure
• Normally, double-helix
• Twisted ribbon
• Base pairing
• AT and GC

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2 strands of DNA

• Orientation
• Every (D/R)NA chain has a 5 and a 3 end
• Position of free attachment pt in sugar
• Many biological processes go from 5 to 3
• Elongation nucleotides added to 3 end
• Read-out DNA-gtRNA-gtprotein

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Orientation the double helix

• Double helix is anti-parallel
• 5 end of each strand at 3 end of the other
• 5 to 3 motion in one strand is 3 to 5 in the
  other
• Double helix has no orientation
• Biology has no forward and reverse strand
• Both strands are equal
• Relative to any single strand, there is a
  reverse complement or reverse strand
• 5TTTTACAGGACCATG 3
• 3AAAATGTCCTGGTAC 5? 5CATGGTCCTGTAAAA 3

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RNA

• Normally single-stranded
• Much less stable than DNA. Shorter lifetime.
• Can form complex structure by self-base-pairing

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RNA self-base-pairing
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DNA ? mRNA ? Protein

• RNA polymerase transcribes a segment of DNA to a
  complementary messenger RNA
• In eukaryotic cells
• Primary messenger RNA is processed to create
  mature mRNA
• this processing involves splicing out certain
  segments of the RNA called introns
• mature mRNA then transported out of the nucleus
• Mature mRNA is translated into protein
• by a ribosome

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3D shape of transfer RNA
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Quicktime animation
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RNA Processing
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RNA splicing

• Splice sites are encoded in the sequence.
• Splice site recognition is complex and imperfect.

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Splice sites
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Gene structure

• Genes are highly structured regions of DNA
• that ultimately yield a strand of amino acids

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Translation of mRNA to Protein

• DNA mRNA represent protein sequences via a
  3-letter code
• there are 3 possible reading frames

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Translation of mRNA to Protein

• Each triplet is called a codon
• The code is degenerate
• 61 codons map to 20 amino acids
• Between 1 and 6 codons per amino acid
• 3 codons stop translation (TAA, TGA, TAG)
• Codons for the same amino acid are called
  synonymous
• DNA mutations that do not change the amino acid
  are called silent

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Fun animations
Quicktime animation Protein synthesis
Quicktime Animation mRNA life cycle
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Non-coding RNA

• Functions
• Transfer RNAs codon-to-amino-acid adapters
• Ribosomes catalyze amino acid linkage
• Protein-RNA complex. RNA is catalytic!
• Small RNAs editing specific mRNAs, or
• Prevent translation of specific mRNAs
• All transcribed from DNA but not translated
• Structure
• Shape, determined by self-pairing, is essential
• External base-pairing is usually essential, too

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Genes

• Molecular definition
• Regions of DNA that are transcribed into a single
  RNA strand, with nearby DNA regions controlling
  time and quantity of transcription
• Protein-coding genes and ncRNA genes
• Classical definition
• Whatever it is that gives rise to a heritable
  trait

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DNA Packaging

• DNA is packed hierarchically
• The chromosome is the largest package
• Width 50 times that of smallest transistor
• Humans have 22 chrs 2 sex chrs
• Human genome 1-2m long 0.34nm/base
• DNA is 1 picogram (10-12g) per gigabase

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Genome sizes

• Widely varied
• Not well correlated with organism
  complexity/sophistication
• Typical bacterium 1-10 megabases (mb)
• Typical single-celled eukaryote 10-30 mb
• Smallest plants and animals 100 mb (fruit fly,
  worm, mustard weed)
• Human 3 gb some rats gophers 5-6 gb
• Pine tree 60 g Fern is 160 gb

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--------------------------------------------------
--------- Organism
Genome size ------------------------------
----------------------------- Amoeba dubia
670,000,000,000 Amoeba
proteus
290,000,000,000 Ophioglossum petiolatum
160,000,000,000 Protopterus aethiopicus
139,000,000,000 Lilium
longiflorum
90,000,000,000 Pinus resinosa
68,000,000,000 Lilium formosanum
36,000,000,000 Paramecium
caudatum
8,600,000,000 Tarsius syrichta
5,151,600,000 Cercopithecus cephus
5,141,700,000 Zea mays
5,000,000,000 Hordeu
m vulgare
5,000,000,000 Macropus robustus
4,396,600,000 Parameles gunni
4,357,200,000 Monodelphis
dimidiata
4,115,400,000 Pongo pygmaeus
4,046,300,000 Gerbillus pyramidum
3,913,100,000 Cercopithecus
aethiops tantalus
3,898,300,000 Galago alleni
3,878,500,000 Didelphis marsupialis
aurita 3,848,900,000 Ctenomys
conoveri
3,848,900,000 Cebus capucinus
3,829,200,000 Ctenomys leucodon
3,824,200,000 Nicotiana
tabaccum
3,800,000,000 Pan troglodytes
3,799,600,000