lecture 2 molecular biology primer saurabh sinha
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Lecture 2Molecular Biology Primer
Saurabh Sinha
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Heredity and DNA
• Heredity: children resemble parents– Easy to see– Hard to explain
• DNA discovered as the physical (molecular) carrier of hereditary information
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Life, Cells, Proteins
• The study of life the study of cells
• Cells are born, do their job, duplicate, die
• All these processes controlled by proteins
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Protein functions
• “Enzymes” (catalysts)– Control chemical reactions in cell – E.g., Aspirin inhibits an enzyme that produces the
“inflammation messenger”
• Transfer of signals/molecules between and inside cells– E.g., sensing of environment
• Regulate activity of genes
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DNA
• DNA is a molecule: deoxyribonucleic acid
• Double helical structure (discovered by Watson, Crick & Franklin)
• Chromosomes are densely coiled and packed DNA
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SOURCE: http://www.microbe.org/espanol/news/human_genome.asp
Chromosome
DNA
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The DNA Molecule
G -- C A -- T T -- A G -- C C -- G G -- C T -- A G -- C T -- A T -- A A -- T A -- T C -- G T -- A
Base = Nucleotide
5’
3’
Base pairing property
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Protein
• Protein is a sequence of amino-acids
•
• 20 possible amino acids
• The amino-acid sequence “folds” into a 3-D structure called protein
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Protein Structure
Protein
DNA
The DNA repair protein MutY (blue) bound to DNA (purple).
PN
AS
cover, courtesy Am
ie B
oal
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SRC:http://www.biologycorner.com/resources/DNA-RNA.gif
Cell
From DNA to Protein: In picture
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From DNA to Protein: In words1. DNA = nucleotide sequence
• Alphabet size = 4 (A,C,G,T)
2. DNA mRNA (single stranded)• Alphabet size = 4 (A,C,G,U)
3. mRNA amino acid sequence• Alphabet size = 20
4. Amino acid sequence “folds” into 3-dimensional molecule called protein
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What about RNA ?
• RNA = ribonucleic acid
• “U” instead of “T”
• Usually single stranded
• Has base-pairing capability– Can form simple non-linear structures
• Life may have started with RNA
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DNA and genes
• DNA is a very “long” molecule – If kept straight, will cover 5cm (!!) in human cell
• DNA in human has 3 billion base-pairs– String of 3 billion characters !
• DNA harbors “genes” – A gene is a substring of the DNA string– A gene “codes” for a protein
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Genes code for proteins
• DNA mRNA protein can actually be written as Gene mRNA protein
• A gene is typically few hundred base-pairs (bp) long
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Transcription
• Process of making a single stranded mRNA using double stranded DNA as template
• Only genes are transcribed, not all DNA
• Gene has a transcription “start site” and a transcription “stop site”
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Step 1: From DNA to mRNA
Transcription
SOURCE: http://www.fed.cuhk.edu.hk/~johnson/teaching/genetics/animations/transcription.htm
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Translation
• Process of making an amino acid sequence from (single stranded) mRNA
• Each triplet of bases translates into one amino acid
• Each such triplet is called “codon”
• The translation is basically a table lookup
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The
Gen
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Cod
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g/at
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s/ge
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htm
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Step 2: mRNA to Amino acid sequence
Translation
SOURCE: http://bioweb.uwlax.edu/GenWeb/Molecular/Theory/Translation/trans1.swf
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Gene structure
SOURCE: http://www.wellcome.ac.uk/en/genome/thegenome/hg02b001.html
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Gene structure
• Exons and Introns– Introns are “spliced” out, and are not part
of mRNA
• Promoter (upstream) of gene
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Gene expression
• Process of making a protein from a gene as template
• Transcription, then translation
• Can be regulated
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Gene Regulation
• Chromosomal activation/deactivation
• Transcriptional regulation
• Splicing regulation
• mRNA degradation
• mRNA transport regulation
• Control of translation initiation
• Post-translational modification
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GENE
ACAGTGA
TRANSCRIPTIONFACTOR
PROTEIN
Transcriptional regulation
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GENE
ACAGTGA
TRANSCRIPTIONFACTOR
PROTEIN
Transcriptional regulation
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The importance of gene regulation
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Genetic regulatory network controlling the development of the body plan of the sea urchin embryoDavidson et al., Science, 295(5560):1669-1678.
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• That was the “circuit” responsible for development of the sea urchin embryo
• Nodes = genes
• Switches = gene regulation
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Genome• The entire sequence of DNA in a cell
• All cells have the same genome– All cells came from repeated duplications starting
from initial cell (zygote)
• Human genome is 99.9% identical among individuals
• Human genome is 3 billion base-pairs (bp) long
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Genome features• Genes
• Regulatory sequences
• The above two make up 5%of human genome
• What’s the rest doing?– We don’t know for sure
• “Annotating” the genome– Task of bioinformatics
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Some genome sizesOrganism Genome size (base pairs)Virus, Phage Φ-X174; 5387 - First sequenced genomeVirus, Phage λ 5×104
Bacterium, Escherichia coli 4×106
Plant, Fritillary assyrica 13×1010 Largest known genomeFungus,Saccharomyces cerevisiae 2×107
Nematode, Caenorhabditis elegans 8×107
Insect, Drosophila melanogaster 2×108
Mammal, Homo sapiens 3×109
Note: The DNA from a single human cell has a length of ~1.8m.
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Evolution
• A model/theory to explain the diversity of life forms
• Some aspects known, some not– An active field of research in itself
• Bioinformatics deals with genomes, which are end-products of evolution. Hence bioinformatics cannot ignore the study of evolution
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“… endless forms most beautiful and most wonderful …”
- Charled Darwin
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Evolution
• All organisms share the genetic code• Similar genes across species • Probably had a common ancestor• Genomes are a wonderful resource to
trace back the history of life• Got to be careful though -- the
inferences may require clever techniques
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Evolution
• Lamarck, Darwin, Weissmann, Mendel
“Oh my dear, let us hope that what Mr. Darwin says is
not true .But if it is true, let us hope
that it will not become generally known”!
Theory wasn’t well-received