Scribed by: Olga RussakovskyCS262: Lecture 1I. IntroductionAll information about the class can be found at cs262.stanford.edu. It is useful to note thestaff’s office hours (Professor Batzoglou: Tue 4:15-5:30, George: Wed 4-6, Andreas: Thu 12:30-2:30) and that the first half hour of the Wednesday and Thursday’s slots will be devotedprimarily to SCPD students. During the TA’s hours, they can also be reached via AIM and phoneas needed (all details are on the website).There is a mailing list set up through Axess and a newsgroup su.class.cs262 which is notmonitored. There will be an optional but useful section every Friday.II. Biological BackgroundA. The Birth of Molecular BiologyThere are many words to describe the field now: bioinformatics, molecular biology,computational genomics. 50 years ago, there was no such area of research; biologists weremainly studying individual animals. It is now believed that the field began with the discovery ofthe double-helix structure of the DNA molecule, by the ornithologist Watson and physicistCrick.DNA is a macromolecule which contains all necessary information for an organism togrow, develop and reproduce. The structure of a strand of DNA and an individual nucleotide arediagramed below.Figure 1. The double-stranded structure of a DNA molecule.Figure 2. Diagram of a nucleotide. The sugar and phosphate group are always the same forall nucleotides, but there are four possible nitrogenous bases – adenine (A), cytosine (C),guanine (G), and thymine (T).DNA is a two-stranded macromolecule composed of nucleotides. The order of nucleotides onone strand can be inferred from the order on the other, because the nucleotides are always coupled Ato T, T to A, G to C and C to G.Thus since a strand of DNA is some sequence of 4 different types ofletters, the DNA molecule can be thought of as a book of letters, where each letter can be encodedusing2 bits of information. The double-stranded structure of DNA both stabilizes it and allows it tobe easily opened and copied.Bioinformatics has come a long way since Watson and Crick’s discovery, and is emerging tostand as a field on its own, not as a combination of biology and computer science, in the 21stcentury.B. DNA to RNA to Protein to CellThere is a natural cycle, diagramed below, which occurs in nature.Figure 3. The various stages in the process of converting DNA to a functional organismDNA holds the genetic information that each organism needs to live and reproduce. Inhumans, DNA is about 3x109nucleotides long, and contains roughly 22,000 genes. DNA isstored within the nucleus of a cell. By a process known as transcription, DNA is converted tomRNA, which is a slightly different molecule and which will be discussed in more detail later.mRNA is then transported into the cell’s cytoplasm to be translated into a sequence of aminoacids, which fold into a 3-D structure to become a functional protein. Proteins are main buildingblocks of life, and they perform most functions within a cell. These cells working together makeup a living organism.C. DNA and RNAAs described above, DNA is a two-stranded molecule composed of 4 differentnucleotides, adenine (A), cytosine (C), guanine (G), and thymine (T), which are paired C—G andA—T. DNA has a double-helix shape in 3D. RNA is a single-stranded molecule similar to DNA,except that thymine is replaced by a different nucleotide, uracil (U).D. ProteinsProteins are a different kind of macromolecule from DNA and RNA. They are composedof a chain of amino acids, which are molecules structured as in the diagram below.Figure 4. The structure of an amino acid.There are 20 different possible R-groups, and thus 20 distinct amino acids with differentproperties. Proteins are composed of approximately 300 to 1000 amino acids, but with largedeviation possible. Amino acids are connected via peptide bonds.Figure 5. Formation of a peptide bond, connecting two amino acids together. The blue box on theright is the peptide bond itself.Amino acid chains then fold into complex 3-D structures, which perform certainfunctions within the cell. The structure of a protein is intimately connected to its function. Thegeneral dogma is that same sequence implies same structure, i.e. that the amino acid sequencehas all the information necessary to predict the 3D structure of the protein and thus to predict itsfunction. However, predicting structure from sequence is still an area of extensive research.This conversion from DNA, containing many genes, to mRNA, containing informationfor only one gene, to an amino acid chain corresponding to that gene and to a functional 3Dstructure is the Central Dogma of Molecular Biology.E. DNA in action: Transcription and TranslationDNA is the carrier of vital information for the organism. The two main questions about itare “how is the information stored in DNA” and “how is this stored information used.” Ingeneral terms, information is stored as nucleotide sequences, as described above, and used inprotein synthesis.As mentioned in previous sections, DNA is contained in the nucleus of the cell. A stretchof it unwinds and its message (or sequence) is transcribed onto a molecule of mRNA. Itsdestination is a molecular workbench in the cytoplasm, a structure called a ribosome, whichtranslates the mRNA to a protein.During translation, each triplet of nucleotides in RNA maps to an amino acid. The tripletsare known as codons. Thus one can think of the sequence AUGCCGGGAGUAUAG in RNA asAUG-CCG-GGA-GUA-UAG for the purposes of translation.Some useful terms to remember are gene, which is a length of DNA that codes for aprotein, and genome, which is the entire DNA sequence within the nucleus.1. Genetic code used in translationTranslation occurs in a very precise manner, with each triplet of nucleotidescorresponding to one specific amino acid.Figure 6. Map of codons to amino acids.Note that since there are 64 different codons (43), but only 20 different amino acids,sometimes as many as 4 different codons code for the same amino acid. However, on the otherhand, some amino acids (such as tryptophan) still have only one codon representation.Also, there are 4 special codons, highlighted in yellow and orange on the diagram above,which do not code for amino acids. UAA, UAG and UGA are stop codons, signaling theribosome to stop translation. AUG, on the other hand, is a start codon, or the place wheretranslation begins.2. Key steps in transcriptionBut before translation of RNA
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