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Lecture 2Molecular Biology Primer
Saurabh Sinha
Heredity and DNA
• Heredity: children resemble parents– Easy to see– Hard to explain
• DNA discovered as the physical (molecular)carrier of hereditary information
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
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
DNA
• DNA is a molecule: deoxyribonucleic acid
• Double helical structure (discovered byWatson, Crick & Franklin)
• Chromosomes are densely coiled andpacked DNA
SOURCE: http://www.microbe.org/espanol/news/human_genome.asp
Chromosome
DNA
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
Protein
• Protein is a sequence of amino-acids•• 20 possible amino acids
• The amino-acid sequence “folds” into a 3-Dstructure called protein
Protein Structure
Protein
DNA
The DNA repair protein MutY (blue) bound to DNA (purple).
PNAS cover, courtesy A
mie Boal
SRC:http://www.biologycorner.com/resources/DNA-RNA.gif
Cell
From DNA to Protein: In picture
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
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
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
Genes code for proteins
• DNA → mRNA → protein can actuallybe written as Gene → mRNA → protein
• A gene is typically few hundred base-pairs (bp) long
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”
Step 1: From DNA to mRNA
Transcription
SOURCE: http://www.fed.cuhk.edu.hk/~johnson/teaching/genetics/animations/transcription.htm
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
The
Gen
etic
Cod
e
SO
UR
CE
:ht
tp://
ww
w.b
iosc
ienc
e.or
g/at
lase
s/ge
neco
de/g
enec
ode.
htm
Step 2: mRNA to Amino acid sequence
Translation
SOURCE: http://bioweb.uwlax.edu/GenWeb/Molecular/Theory/Translation/trans1.swf
Gene structure
SOURCE: http://www.wellcome.ac.uk/en/genome/thegenome/hg02b001.html
Gene structure
• Exons and Introns– Introns are “spliced” out, and are not part of
mRNA
• Promoter (upstream) of gene
Gene expression
• Process of making a protein from agene as template
• Transcription, then translation
• Can be regulated
Gene Regulation
• Chromosomal activation/deactivation• Transcriptional regulation• Splicing regulation• mRNA degradation• mRNA transport regulation• Control of translation initiation• Post-translational modification
GENE
ACAGTGA
TRANSCRIPTIONFACTOR
PROTEIN
Transcriptional regulation
GENE
ACAGTGA
TRANSCRIPTIONFACTOR
PROTEIN
Transcriptional regulation
The importance of generegulation
Genetic regulatory network controlling the development of the body plan of the sea urchin embryoDavidson et al., Science, 295(5560):1669-1678.
• That was the “circuit” responsible fordevelopment of the sea urchin embryo
• Nodes = genes• Switches = gene regulation
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
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
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.
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
“… endless forms most beautiful and most wonderful …”- Charled Darwin
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
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