Download Lecture-1-molbio

CMSC 828N Introduction:
Molecular biology background
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
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Cell contents: small molecules
Examples:
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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.,
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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 cell’s 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
• A:T and G:C
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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->RNA->protein
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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”
5’TTTTACAGGACCATG 3’
3’AAAATGTCCTGGTAC 5’ 5’CATGGTCCTGTAAAA 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
Hordeum 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
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