Basic Molecular Biology Many slides by Omkar Deshpande

Overview Structures of biomolecules Central Dogma of Molecular Biology Overview of this course Computer scientists vs Biologists

Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Medicine and Society: A 2001 Primer, 2001

Watson and Crick

Macromolecule (Polymer) Monomer DNADeoxyribonucleotides (dNTP) RNARibonucleotides (NTP) Protein or PolypeptideAmino Acid

Nucleic acids (DNA and RNA) Form the genetic material of all living organisms. Found mainly in the nucleus of a cell (hence “nucleic”) Contain phosphoric acid as a component (hence “acid”) They are made up of nucleotides.

Nucleotides Phosphate Group Sugar Nitrogenous Base Phosphate Group Sugar Nitrogenous Base

T C A C T G G C G A G T C A G C DNA A = T G = C

The gene and the genome Genome = The entire DNA sequence within the nucleus. The information in the genome is used for protein synthesis A gene is a length of DNA that codes for a (single) protein.

How big are genomes? OrganismGenome Size (Bases)Estimated Genes Human (Homo sapiens)3 billion30,000 Laboratory mouse (M. musculus) 2.6 billion30,000 Mustard weed (A. thaliana)100 million25,000 Roundworm (C. elegans)97 million19,000 Fruit fly (D. melanogaster)137 million13,000 Yeast (S. cerevisiae)12.1 million6,000 Bacterium (E. coli) 4.6 million3,200 Human immunodeficiency virus (HIV) 97009

Repeats The DNA is full of repetitive elements (those that occur over & over & over) There are several type of repeats, including SINEs & LINEs (Short & Long Interspersed Elements) (1 million just ALUs) and low complexity elements. Their function is poorly understood, but they make problems more difficult.

Central dogma DNA tRNA rRNA snRNA mRNA transcription translation POLYPEPTIDE ZOOM IN

Transcription The DNA is contained in the nucleus of the cell. A stretch of it unwinds there, and its message (or sequence) is copied onto a molecule of mRNA. The mRNA then exits from the cell nucleus.

T C A C T G G C G A G T C A G C G A G U C A G C DNARNA A = T G = C T  U

More complexity The RNA message is sometimes “edited”. Exons are nucleotide segments whose codons will be expressed. Introns are intervening segments (genetic gibberish) that are snipped out. Exons are spliced together to form mRNA.

Splicing frgjjthissentencehjfmkcontainsjunkelm thissentencecontainsjunk

Key player: RNA polymerase It is the enzyme that brings about transcription by going down the line, pairing mRNA nucleotides with their DNA counterparts.

Promoters Promoters are sequences in the DNA just upstream of transcripts that define the sites of initiation. The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated. 5’ Promoter 3’

Promoters Promoters are sequences in the DNA just upstream of transcripts that define the sites of initiation. The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated. 5’ Promoter 3’

Transcription – key steps Initiation Elongation Termination + DNA RNA DNA

Transcription – key steps Initiation Elongation Termination DNA

Transcription – key steps Initiation Elongation Termination DNA

Transcription – key steps Initiation Elongation Termination DNA

Transcription – key steps Initiation Elongation Termination + DNA RNA DNA

Genes can be switched on/off In an adult multicellular organism, there is a wide variety of cell types seen in the adult. eg, muscle, nerve and blood cells. The different cell types contain the same DNA though. This differentiation arises because different cell types express different genes. Promoters are one type of gene regulators

Transcription (recap) The DNA is contained in the nucleus of the cell. A stretch of it unwinds there, and its message (or sequence) is copied onto a molecule of mRNA. The mRNA then exits from the cell nucleus. Its destination is a molecular workbench in the cytoplasm, a structure called a ribosome.

Translation How do I interpret the information carried by mRNA to the Ribosome? Think of the sequence as a sequence of “triplets”. Think of AUGCCGGGAGUAUAG as AUG- CCG-GGA-GUA-UAG. Each triplet (codon) maps to an amino acid.

The Genetic Code f : codon  amino acid 1968 Nobel Prize in medicine – Nirenberg and Khorana Important – The genetic code is universal! It is also redundant / degenerate.

The Genetic Code

Composed of a chain of amino acids. R | H 2 N--C--COOH | H Proteins 20 possible groups

R R | | H 2 N--C--COOH H 2 N--C--COOH | | H H Proteins

Dipeptide R O R | II | H 2 N--C--C--NH--C--COOH | | H H This is a peptide bond

Protein structure Linear sequence of amino acids folds to form a complex 3-D structure. The structure of a protein is intimately connected to its function. The 3-D shape of proteins gives them their working ability – the ability to bind with other molecules.

Our course (2427) DNA rRNA snRNA mRNA transcription translation POLYPEPTIDE Part 1, DNA: Assembly, Evolution, Alignment Part 2, Genes: Prediction, Regulation Part 3, Structures & Interactions

Computer Scientists vs Biologists (courtesy Steven Skiena, SUNY Stony Brook)

Computer scientists vs Biologists Biologists strive to understand the very complicated, very messy natural world. Computer scientists seek to build their own clean and organized virtual worlds.

Computer scientists vs Biologists Computer scientists get high-paid jobs after graduation. Biologists typically have to complete one or more post-docs...

Computer scientists vs Biologists Nothing is ever completely true or false in Biology. Everything is either true or false in computer science.