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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 andinside 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 byWatson, Crick & Franklin)
• Chromosomes are densely coiled andpacked 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 -- CA -- TT -- AG -- CC -- GG -- CT -- AG -- CT -- AT -- AA -- TA -- TC -- GT -- 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-Dstructure called protein
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Protein Structure
Protein
DNA
The DNA repair protein MutY (blue) bound to DNA (purple).
PNAS cover, courtesy A
mie Boal
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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 actuallybe 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 mRNAusing double stranded DNA as template
• Only genes are transcribed, not all DNA
• Gene has a transcription “start site” and atranscription “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 sequencefrom (single stranded) mRNA
• Each triplet of bases translates into oneamino acid
• Each such triplet is called “codon”
• The translation is basically a table lookup
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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 agene 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 generegulation
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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 fordevelopment 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 amongindividuals
• 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 lifeforms
• Some aspects known, some not– An active field of research in itself
• Bioinformatics deals with genomes, which areend-products of evolution. Hence bioinformaticscannot 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 clevertechniques
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Evolution
• Lamarck, Darwin, Weissmann, Mendel
“Oh my dear, let us hopethat what Mr. Darwin says is
not true.But if it is true, let us hope
that it will not becomegenerally known!”
Theory wasn’t well-received