Lecture 2Molecular Biology PrimerSaurabh SinhaHeredity and DNA• Heredity: children resemble parents– Easy to see– Hard to explain• DNA discovered as the physical (molecular)carrier of hereditary informationLife, Cells, Proteins• The study of life ⇔ the study of cells• Cells are born, do their job, duplicate, die• All these processes controlled by proteinsProtein 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 genesDNA• DNA is a molecule: deoxyribonucleic acid• Double helical structure (discovered byWatson, Crick & Franklin)• Chromosomes are densely coiled andpacked DNASOURCE: http://www.microbe.org/espanol/news/human_genome.aspChromosomeDNAThe DNA MoleculeG -- CA -- TT -- AG -- CC -- GG -- CT -- AG -- CT -- AT -- AA -- TA -- TC -- GT -- A≡Base = Nucleotide5’3’Base pairing propertyProtein• Protein is a sequence of amino-acids•• 20 possible amino acids• The amino-acid sequence “folds” into a 3-Dstructure called proteinProtein StructureProteinDNAThe DNA repair protein MutY (blue) bound to DNA (purple). PNAS cover, courtesy Amie BoalSRC:http://www.biologycorner.com/resources/DNA-RNA.gifCellFrom DNA to Protein: In pictureFrom 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 = 204. Amino acid sequence “folds” into 3-dimensional molecule called proteinWhat 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 RNADNA 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 proteinGenes code for proteins• DNA → mRNA → protein can actuallybe written as Gene → mRNA → protein• A gene is typically few hundred base-pairs (bp) longTranscription• 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 mRNATranscriptionSOURCE: http://www.fed.cuhk.edu.hk/~johnson/teaching/genetics/animations/transcription.htmTranslation• 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 lookupThe Genetic CodeSOURCE:http://www.bioscience.org/atlases/genecode/genecode.htmStep 2: mRNA to Amino acid sequenceTranslationSOURCE: http://bioweb.uwlax.edu/GenWeb/Molecular/Theory/Translation/trans1.swfGene structureSOURCE: http://www.wellcome.ac.uk/en/genome/thegenome/hg02b001.htmlGene structure• Exons and Introns– Introns are “spliced” out, and are not part ofmRNA• Promoter (upstream) of geneGene expression• Process of making a protein from agene as template• Transcription, then translation• Can be regulatedGene Regulation• Chromosomal activation/deactivation• Transcriptional regulation• Splicing regulation• mRNA degradation• mRNA transport regulation• Control of translation initiation• Post-translational modificationGENEACAGT GATRANSCRIPT I ONFACTORPROTEINTranscriptional regulationGENEACAGT GATRANSCRIPT I ONFACTORPROTEINTranscriptional regulationThe importance of generegulationGenetic 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 regulationGenome• The entire sequence of DNA in a cell• All cells have the same genome– All cells came from repeated duplications startingfrom initial cell (zygote)• Human genome is 99.9% identical amongindividuals• Human genome is 3 billion base-pairs (bp) longGenome 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 bioinformaticsSome genome sizesOrganism Genome size (base pairs)Virus, Phage Φ-X174; 5387 - First sequenced genomeVirus, Phage λ 5×104Bacterium, Escherichia coli4×106Plant, Fritillary assyrica13×1010 Largest known genomeFungus,Saccharomyces cerevisiae2×107Nematode, Caenorhabditis elegans8×107Insect, Drosophila melanogaster2×108Mammal, Homo sapiens3×109Note: 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 DarwinEvolution• All organisms share the genetic code• Similar genes across species• Probably had a common ancestor• Genomes are a wonderful resource totrace back the history of life• Got to be careful though -- theinferences may require clevertechniquesEvolution• Lamarck, Darwin, Weissmann, Mendel“Oh my dear, let us hopethat what Mr. Darwin says isnot true.But if it is true, let us hopethat it will not becomegenerally known!”Theory wasn’t