(Really) Basic Molecular Biology James A. Foster U. Idaho, IBEST

Overview Intro to subject and course Problems being addressed Translation: turning DNA into living things DNA to RNA to proteins Regulating expression Types of DNA Proteins Evolution: changing living things Errors Phylogeny

Bioinformatics & Comp. Bio. Bioinformatics: developing tools and techniques for storing and analyzing data from molecular biology Computational biology: bioinorganic plus simulations and modeling This course covers a narrow slice of bioinformatics (despite the course title)

Pop Quiz!! (5 minutes) Please write a paragraph on each of the following: What you hope to get out of this class What you know that you can contribute What you don’t know that you wish you did

Course Details Web page has assignments, readings, discussions, extra materials—refer to it often: www.cs.uidaho.edu/~foster/CurrentClasses/cs504 Syllabus, office hours, notes on webpage 3 exams, regular homework, discussion, presentations (grads) Books: why these, what about others? The Web: use it You will want Unix accounts

What Problem Are We Solving? Biology: Polymers In space Interact For life Data: Sequences Structures Graphs

Examples of Questions What known data (sequences, structures, graphs) are similar to mine? What biological purpose do my molecules have? How do my molecules work? Where did my molecules come from?

The Central Dogma Copyright 1999 Access Excellence @ the National Health Museum.

DNA, RNA and proteins See page 162 of BCS Backbone Nucleotides: A, C, G, T Base pairing: A-T, G-C Two strands, connected by base pairing and listed 5’ to 3’ in double helix Then wadded into tight little balls Sometimes grouped into chromosomes

DNA: Illustration Copyright 1999 Access Excellence @ the National Health Museum.

DNA Replication

DNA, RNA and proteins Just like DNA, except: Slighly different backbone U instead of T only one strand, which folds in on itself

DNA, RNA and proteins Backbone Side chain of amino acids (aka residues) 20 available Different chemical properties Structures: alpha coils, beta sheets Where the action is: interact with other molecules (DNA, RNA, proteins)

Protein Structure Copyright 1999 Access Excellence @ the National Health Museum.

Binding sites Copyright 1999 Access Excellence @ the National Health Museum.

Cells: where it all happens Copyright 1999 Access Excellence @ the National Health Museum.

DNA to RNA Enzymes (e.g. relaxase) unwind DNA Enzymes (e.g. rna synthetase) makes complementary pre-mRNA (AU, CG, G  C, T  A) Enzymes edit pre-mRNA to get mRNA: removing introns, rearranging exons, correcting errors, etc.

RNA to proteins Ribosome (a protein) binds to RNA at start codon (usually AUG) Reads 3-nucleotide codon in appropriate Open Reading Frame (ORF) Binds to tRNA, which is linked to amino acid (determined by genetic code) Transfers tRNA residue to growing protein Moves to next codon Detaches at stop codon (UAA, UAG, or UGA)

The genetic code Copyright 1999 Access Excellence @ the National Health Museum.

Steps during translation Copyright 1999 Access Excellence @ the National Health Museum.

Protein Synthesis Copyright 1999 Access Excellence @ the National Health Museum.

Proteins to Life The new protein Folds as determined by chemystery Is transported to appropriate place (in, on, or outside of cell membrane or equivalent) Binds to its target Changes conformation And the magic continues…

Types of DNA Genomic Non-genomic Genic: codes for proteins for the host (30K in humans, 100K proteins) Non-Genic (95% of humans) RNA coding Regulatory Mobile elements (over 40% of humans) Endogenous retroviruses Non-genomic Organelles (mitochondria, chloroplasts) Plasmids

Evolution Errors happen: Isolated populations get different errors While transcribing: misreads, slipping, breaks, exon duplication, gene duplication While sitting in the cell: rearrangements, chromosomal duplication From the outside: viruses, mobile elements Isolated populations get different errors We observe only those differences that persist Because they actually help (selection) Or just because (neutral evolution)