Molecular Biology Primer for CS and engineering students Alan Qi January, 2010
CS69000 Advanced Bioinformatics • Content description: This seminar course will include lectures by the instructor, presentations of readings by students, and guest lectures by invited speakers. Students will be expected to present at least one major paper during the term. This course covers statistical learning algorithms for computational and systems biology and studies important research problems in these areas, with a focus on biological network modeling and analysis.
Topics • Biological problems including motif discovery, gene expression analysis, biological network reconstruction, network analysis, and phylogenetics.Fundamental algorithmic techniques including hidden Markov models, exponential-family random graph models (ERGM), hierarchical clustering by hierarchical Dirichlet processes, Generalized belief propagation, Markov networks, structure learning for network models, and approximate inference on graphical models
Grading policy • Class participation: 15% • Class presentations: 25% • Papers evaluations: 30% • Research project: 30% • Preliminary report: 5% • Class presentation: 5% • Final report: 20%
Project report • You are encouraged to collaborate on the project. We expect a four page write-up about the project, which should clearly and succinctly describe the project goal, methods, and your results. Each group should submit only one copy of the write-up and describe the contributions of each group member to the project. A two person group will have 6 pages, a three person group will have 8 pages, and so on.
Central Dogma DNA RNA Protein
Genes control the making of cell parts • The gene is a fundamental unit of inheritance – DNA molecule contains tens of thousands of genes – Each gene governs the making of one functional element, one “part” of the cell machine – Every time a “part” must be made, a piece of the genome is copied, transported, and used as a blueprint • RNA is a temporary copy – The medium for transporting genetic information from the DNA information repository to the protein-making machinery is an RNA molecule – The more parts are needed, the more copies are made – Each mRNA only lasts a limited time before degradation
From pre-mRNA to mRNA: Splicing • In some species (e.g. eukaryotes), not every part of a gene is coding – Functional exons interrupted by non-translated introns – During pre-mRNA maturation, introns are spliced out – In humans, primary transcript can be 106 bp long – Alternative splicing can yield different exon subsets for the same gene, and hence different protein products
eukaryotes and prokaryotes • Eukaryotes include animals, plants and fungis. organisms whose cells are organized into complex structures enclosed within membranes. The defining membrane-bound structure that differentiates eukaryotic cells from prokaryotic cells is the nucleus. • The presence of a nucleus gives these organisms their name, which comes from the Greek ευ (eu), meaning "good/true," and κάρυον (karyon), "nut.“ http://en.wikipedia.org/wiki/Eukaryote
RNA can be functional • Single Strand allows complex structure – Self-complementary regions form helical stems – Three-dimensional structure allows functionality of RNA • Active research area: non-coding RNAs… – Once upon a time, before DNA and protein, RNA did all
Central Dogma DNA RNA Protein
Condon • The genetic code defines a mapping between tri-nucletide sequences called codons and amino acids. • Condon is defined by the initial nucleotide from which translation starts. • For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA and CCC; and if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. • Every sequence can thus be read in three reading frames. With double-stranded DNA there are six possible reading frames. three in the forward orientation on one strand and three reverse (on the opposite strand). • If the DNA is eukaryotic, the reading frame may contain introns. • Start/stop codons Translation starts with a chain start codon. The most common start codon is AUG, which codes for methionine, so most amino acid chains start with methionine. Nearby sequences and initiation factors are also required to start translation. Stop condons: UAG-amber, UGA-umber, and UAA-ochre.
Degeneracy of the genetic code • The genetic code has redundancy but no ambiguity. • Both Codons GAA and GAG -> glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). • The codons encoding one amino acid may differ in any of their three positions. • the amino acid glutamic acid is specified by GAA and GAG codons (difference in the third position), • the amino acid leucine is specified by UUA, UUG, CUU, CUC, CUA, CUG codons (difference in the first or third position) • the amino acid serine is specified by UCA, UCG, UCC, UCU, AGU, AGC (difference in the first, second or third position).
Proteins carry out the cell’s chemistry • More complex polymer – Nucleic Acids have 4 building blocks – Proteins have 20. Greater versatility – Each amino acid has specific properties • Sequence -> Structure -> Function – The amino acid sequence determines the three-dimensional fold of protein – The protein’s function largely depends on the features of the 3D structure • Proteins play diverse roles – Catalysis, binding, cell structure, signaling, transport, metabolism
Protein structures • Primary structure - the amino acid sequence of the peptide chains. • Secondary structure - highly regular sub-structures (alpha helix and strands of beta sheet) which are locally defined, meaning that there can be many different secondary motifs present in one single protein molecule. • Tertiary structure - Three-dimensional structure of a single protein molecule; a spatial arrangement of the secondary structures. • Quaternary structure - complex of several protein molecules or polypeptide chains, usually called protein subunits in this context, which function as part of the larger assembly or protein complex.