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Stanford CS 262 - Lecture 2 - A Zero-Knowledge Based Introduction to Biology

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CS262BiologyHow to learn some?The CellHow many?ChromosomesSlide 7Nucleotide“AGACC” (backbone)“AGACC” (DNA)DNA is double strandedRNASlide 13Genes & ProteinsSlide 15Gene TranscriptionSlide 17Slide 18Slide 19Slide 20RNA ProcessingGene StructureSlide 23Amino acidProteinsTranslationThe Genetic CodeTranslation (tRNA)Slide 29Slide 30Slide 31Slide 32Errors?Reading FramesSynonymous MutationMissense MutationNonsense MutationFrameshiftQuality ControlGene Expression RegulationRegulatory MechanismsAssembliesRetrovirusInfectionSlide 45Replication cycleSlide 47Are they alive?Slide 49Slide 50The end?KeywordsCS262CS262A Zero-Knowledge Based Introduction to BiologyBiologyBiologyFrom the greek word βίος = lifeTimeline:1683 – discovery of bacteria1858 – Darwin’s natural selection1865 – Mendel’s laws1953 – double helix suggested by Watson-Crick1955 – discovery of DNA and RNA polymerase1978 – sequencing of first genome (5kb virus)1983 – invention of PCR1990 – discovery of RNAi2000 – human genome (draft)How to learn some?How to learn some?Online sourcesWikipediahttp://www.wikipedia.org/John Kimball’s Biology Pageshttp://biology-pages.info/Cold Spring Harbor MeetingsCSHL Biology of GenomesCSHL Genome InformaticsHang out with biologistsThe CellThe Cell© 1997-2005 Coriell Institute for Medical Research cell, nucleus, cytoplasm, mitochondrionHow many?How many?Cells in the human body:~1014 (100 trillion)~1015 bacterial cells!ChromosomesChromosomeshistone, nucleosome, chromatin, chromosome, centromere, telomereH1DNAH2A, H2B, H3, H4~146bptelomerecentromerenucleosomechromatinHow many?How many?Chromosomes in a human cell:46 (2x22 + X/Y)NucleotideNucleotideOC CCCHHHHHHHCOPOO-Oto next nucleotideto previous nucleotideto basedeoxyribose, nucleotide, base, A, C, G, T, purine, pyrimidine, 3’, 5’3’5’Adenine (A)Cytosine (C)Guanine (G)Thymine (T)Let’s write “AGACC”!pyrimidinespurines““AGACC” (backbone)AGACC” (backbone)““AGACC” (DNA)AGACC” (DNA)deoxyribonucleic acid (DNA)5’5’3’3’DNA is double strandedDNA is double stranded3’5’5’3’DNA is always written 5’ to 3’AGACC or GGTCTstrand, reverse complementRNARNAOC CCCHOHHHHHHCOPOO-Oto next ribonucleotideto previous ribonucleotideto baseribose, ribonucleotide, U3’5’Adenine (A)Cytosine (C)Guanine (G)Uracil (U)pyrimidinespurinesHow many?How many?Nucleotides in the human genome:~ 3 billionGenes & ProteinsGenes & Proteins3’5’5’3’TAGGATCGACTATATGGGATTACAAAGCATTTAGGGA...TCACCCTCTCTAGACTAGCATCTATATAAAACAGAAATCCTAGCTGATATACCCTAATGTTTCGTAAATCCCT...AGTGGGAGAGATCTGATCGTAGATATATTTTGTCTTAUGGGAUUACAAAGCAUUUAGGGA...UCACCCUCUCUAGACUAGCAUCUAUAUAA(transcription)(translation)Single-stranded RNAproteinDouble-stranded DNAgene, transcription, translation, proteinHow many?How many?Genes in the human genome:~ 20,000 – 25,000Gene TranscriptionGene Transcriptionpromoter3’5’5’3’G A T T A C A . . .C T A A T G T . . .Gene TranscriptionGene Transcriptiontranscription factor, binding site, RNA polymerase3’5’5’3’Transcription factors recognize transcription factor binding sites and bind to them, forming a complex.RNA polymerase binds the complex.G A T T A C A . . .C T A A T G T . . .Gene TranscriptionGene Transcription3’5’5’3’The two strands are separatedG A T T A C A . . .C T A A T G T . . .Gene TranscriptionGene Transcription3’5’5’3’An RNA copy of the 5’→3’ sequence is created from the 3’→5’ templateG A T T A C A . . .C T A A T G T . . .G A U U A C AGene TranscriptionGene Transcription3’5’5’3’G A U U A C A . . . G A T T A C A . . .C T A A T G T . . .pre-mRNA 5’ 3’RNA ProcessingRNA Processing5’ cap, polyadenylation, exon, intron, splicing, UTR, mRNA5’ cappoly(A) tailintronexonmRNA5’ UTR 3’ UTRGene StructureGene Structure5’ 3’promoter5’ UTRexons 3’ UTRintronscodingnon-codingHow many?How many?Exons per gene:~ 8 on average (max: 148)Nucleotides per exon:170 on average (max: 12k)Nucleotides per intron:5,500 on average (max: 500k)Nucleotides per gene:45k on average (max: 2,2M)Amino acidAmino acidamino acidCONHCHH OHRThere are 20 standard amino acidsAlanineArginineAsparagineAspartateCysteineGlutamateGlutamineGlycineHistidineIsoleucineLeucineLysineMethioninePhenylalanineProlineSerineThreonineTryptophanTyrosineValineProteinsProteinsCONHCHRto previous aa to next aaN-terminusH OHC-terminusN-terminus, C-terminusTranslationTranslationThe ribosome synthesizes a protein by reading the mRNA in triplets (codons). Each codon is transl ated to an amino acid. ribosome, codonmRNAP site A siteThe Genetic CodeThe Genetic CodeU C A GU UUU Phenylalanine (Phe) UCU Serine (Ser) UAU Tyrosine (Tyr) UGU Cysteine (Cys) U UUC Phe UCC Ser UAC Tyr UGC Cys C UUA Leucine (Leu) UCA Ser UAA STOP UGA STOP A UUG Leu UCG Ser UAG STOP UGG Tryptophan (Trp) GC CUU Leucine (Leu) CCU Proline (Pro) CAU Histidine (His) CGU Arginine (Arg) U CUC Leu CCC Pro CAC His CGC Arg C CUA Leu CCA Pro CAA Glutamine (Gln) CGA Arg A CUG Leu CCG Pro CAG Gln CGG Arg GA AUU Isoleucine (Ile) ACU Threonine (Thr) AAU Asparagine (Asn) AGU Serine (Ser) U AUC Ile ACC Thr AAC Asn AGC Ser C AUA Ile ACA Thr AAA Lysine (Lys) AGA Arginine (Arg) A AUG Methionine (Met) or START ACG Thr AAG Lys AGG Arg GG GUU Valine (Val) GCU Alanine (Ala) GAU Aspartic acid (Asp) GGU Glycine (Gly) U GUC Val GCC Ala GAC Asp GGC Gly C GUA Val GCA Ala GAA Glutamic acid (Glu) GGA Gly A GUG Val GCG Ala GAG Glu GGG Gly GTranslation (tRNA)Translation (tRNA)tRNA, anticodonCCA(Tryptophan codon: UGG)Tryptophan anticodonTranslation (tRNA)Translation (tRNA)aminoacylationTryptophanAminoacylationCCACCACharged tRNAUnloaded tRNATranslationTranslation5’ . . . A U U A U G G C C U G G A C U U G A . . . 3’UTRMetStart CodonAla Trp ThrTranslationTranslation5’ . . . A U U A U G G C C U G G A C U U G A . . . 3’TranslationTranslationMet Ala5’ . . . A U U A U G G C C U G G A C U U G A . . . 3’TrpErrors?Errors?What if the transcription / translation machinery makes mistakes?What is the effect of mutations in coding regions?mutationReading FramesReading Framesreading frameG C U U G U U U A C G A A U U A GG C U U G U U U A C G A A U U A GG C U U G U U U A C G A A U U A GG C U U G U U U A C G A A U U A GSynonymous MutationSynonymous MutationG C U U G U U U A C G A A U U A GAla Cys Leu Arg IleG C U U G U U U A C G A A U U A Gsynonymous (silent)


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Stanford CS 262 - Lecture 2 - A Zero-Knowledge Based Introduction to Biology

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