2. A short introduction to biology

3. Life Two categories: –Prokaryotes (e.g. bacteria) Unicellular No nucleus –Eukaryotes (e.g. fungi, plant, animal) Unicellular or multicellular Has nucleus

4. Prokaryote vs Eukaryote Eukaryote has many membrane-bounded compartment inside the cell –Different biological processes occur at different cellular location

5. Organism, Organ, Cell Organism Organ

6. Chemical contents of cell Water Macromolecules (polymers) - “strings” made by linking monomers from a specified set (alphabet) –Protein –DNA –RNA –…–… Small molecules –Sugar –Ions (Na +, Ka +, Ca 2+, Cl -,…) –Hormone –…–…

7. DNA DNA: forms the genetic material of all living organisms –Can be replicated and passed to descendents –Contains information to produce proteins To computer scientists, DNA is a string made from alphabet {A, C, G, T} –e.g. ACAGAACGTAGTGCCGTGAGCG Each letter is a nucleotide Length varies from hundreds to billions

8. RNA Historically thought to be information carrier only –DNA => RNA => Protein –New roles have been found for them To computer scientists, RNA is a string made from alphabet {A, C, G, U} –e.g. ACAGAACGUAGUGCCGUGAGCG Each letter is a nucleotide Length varies from tens to thousands

9. Protein Protein: the actual “worker” for almost all processes in the cell –Enzymes: speed up reactions –Signaling: information transduction –Structural support –Production of other macromolecules –Transport To computer scientists, protein is a string made from 20 kinds of characters –E.g. MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGP Each letter is called an amino acid Length varies from tens to thousands

10. DNA/RNA zoom-in Commonly referred to as Nucleic Acid DNA: Deoxyribonucleic acid RNA: Ribonucleic acid Found mainly in the nucleus of a cell (hence “nucleic”) Contain phosphoric acid as a component (hence “acid”) They are made up of a string of nucleotides

11. Nucleotides A nucleotide has 3 components –Sugar ring (ribose in RNA, deoxyribose in DNA) –Phosphoric acid –Nitrogen base Adenine (A) Guanine (G) Cytosine (C) Thymine (T) in DNA and Uracil (U) in RNA

12. G A G T C A G C 5’-AGCGACTG-3’ AGCGACTG Phosphate Sugar Base 1 2 3 4 5 Often recorded from 5’ to 3’, which is the direction of many biological processes. e.g. DNA replication, transcription, etc. 5’ 3’ DNA Free phosphate 5 prime 3 prime

13. G A G U C A G U 5’-AGUGACUG-3’ AGUGACUG Often recorded from 5’ to 3’, which is the direction of many biological processes. e.g. translation. 5’ 3’ RNA Free phosphate 5 prime 3 prime Phosphate Sugar Base 1 2 3 4 5

14. T C A C T G G C G A G T C A G C Base-pair: A = T G = C 5’ 3’ 5’-AGCGACTG-3’ 3’-TCGCTGAC-5’ AGCGACTG TCGCTGAC Forward (+) strand Backward (-) strand One strand is said to be reverse- complementary to the other DNA usually exists in pairs.

15. DNA double helix G-C pair is stronger than A-T pair

16. RNA RNAs are normally single- stranded Form complex structure by self- base-pairing A=U, C=G Can also form RNA-DNA and RNA-RNA double strands. –A=T/U, C=G

17. Carboxyl group Amino group Protein zoom-in Side chain Generic chemical form of amino acid Protein is the actual “worker” for almost all processes in the cell A string built from 20 kinds of chars –E.g. MGDVEKGKKIFIMKCSQCHTVEKGGKH Each letter is called an amino acid R | H 2 N--C--COOH | H

18. 20 amino acids, only differ at side chains –Each can be expressed by three letters –Or a single letter: A-Y, except B, J, O, U, X, Z –Alanine = Ala = A –Histidine = His = H Units of Protein: Amino acid

19. R R | | H 2 N--C--CO--NH--C--COOH | | H H R R | | H 2 N--C--COOH H 2 N--C--COOH | | H H Amino acids => peptide Peptide bond

20. Protein Has orientations Usually recorded from N-terminal to C-terminal Peptide vs protein: basically the same thing Conventions –Peptide is shorter (< 50aa), while protein is longer –Peptide refers to the sequence, while protein has 2D/3D structure R H2N RRRRR COOH N-terminal C-terminal …

21. Genome and chromosome Genome: the complete DNA sequences in the cell of an organism –May contain one (in most prokaryotes) or more (in eukaryotes) chromosomes Chromosome: a single large DNA molecule in the cell –May be circular or linear –Contain genes as well as “junk DNAs” –Highly packed!

22. Formation of chromosome

23. 50,000 times shorter than extended DNA The total length of DNA present in one adult human is the equivalent of nearly 70 round trips from the earth to the sun

24. Gene Gene: unit of heredity in living organisms –A segment of DNA with information to make a protein or a functional RNA

25. Some statistics ChromosomesBasesGenes Human463 billion20k-25k Dog782.4 billion~20k Corn202.5 billion50-60k Yeast1620 million~7k E. coli14 million~4k Marbled lungfish ?130 billion?

27. Human genome 46 chromosomes: 22 pairs + X + Y 1 from mother, 1 from father Female: X + X Male: X + Y

28. Central dogma of molecular biology

29. DNA Replication The process of copying a double-stranded DNA molecule –Semi-conservative 5’-ACATGATAA-3’ 3’-TGTACTATT-5’  5’-ACATGATAA-3’ 3’-TGTACTATT-5’

30. Mutation: changes in DNA base-pairs Proofreading and error-correcting mechanisms exist to ensure extremely high fidelity p p p Nucleotide triphosphate (dNTP)

31. Central dogma of molecular biology

32. Transcription The process that a DNA sequence is copied to produce a complementary RNA –Called message RNA (mRNA) if the RNA carries instruction on how to make a protein –Called non-coding RNA if the RNA does not carry instruction on how to make a protein –Only consider mRNA for now Similar to replication, but –Only one strand is copied

33. Transcription (where genetic information is stored) (for making mRNA) Coding strand: 5’-ACGTAGACGTATAGAGCCTAG-3’ Template strand: 3’-TGCATCTGCATATCTCGGATC-5’ mRNA: 5’-ACGUAGACGUAUAGAGCCUAG-3’ Coding strand and mRNA have the same sequence, except that T’s in DNA are replaced by U’s in mRNA. DNA-RNA pair: A=U, C=G T=A, G=C

34. Translation The process of making proteins from mRNA A gene uniquely encodes a protein There are four bases in DNA (A, C, G, T), and four in RNA (A, C, G, U), but 20 amino acids in protein How many nucleotides are required to encode an amino acid in order to ensure correct translation? –4^1 = 4 –4^2 = 16 –4^3 = 64 The actual genetic code used by the cell is a triplet. –Each triplet is called a codon

35. The Genetic Code Third letter

36. Translation The sequence of codons is translated to a sequence of amino acids Gene: -GCT TGT TTA CGA ATT- mRNA: -GCU UGU UUA CGA AUU - Peptide: - Ala - Cys - Leu - Arg - Ile – Start codon: AUG –Also code Met –Stop codon: UGA, UAA, UAG

37. Translation Transfer RNA (tRNA) – a different type of RNA. –Freely float in the cell. –Every amino acid has its own type of tRNA that binds to it alone. Anti-codon – codon binding crucial. mRNA tRNA-Leu Nascent peptide tRNA-Pro Anti-codon

38. Transcriptional regulation gene promoter Transcription starting site RNA Polymerase Transcription factor Will talk more in later lectures RNA polymerase binds to certain location on promoter to initiate transcription Transcription factor binds to specific sequences on the promoter to regulate the transcription –Recruit RNA polymerase: induce –Block RNA polymerase: repress –Multiple transcription factors may coordinate

39. Splicing gene promoter Transcription starting site Pre-mRNA transcription Pre-mRNA needs to be “edited” to form mature mRNA Will talk more in later lectures. 5’ UTR 3’ UTRexon intron Start codonStop codon Open reading frame (ORF) Pre-mRNA Mature mRNA (mRNA) Splicing

40. Summary DNA: a string made from {A, C, G, T} –Forms the basis of genes –Has 5’ and 3’ –Normally forms double-strand by reverse complement RNA: a string made from {A, C, G, U} –mRNA: messenger RNA –tRNA: transfer RNA –Other types of RNA: rRNA, miRNA, etc. –Has 5’ and 3’ –Normally single-stranded. But can form secondary structure Protein: made from 20 kinds of amino acids –Actual worker in the cell –Has N-terminal and C-terminal –Sequence uniquely determined by its gene via the use of codons –Sequence determines structure, structure determines function Central dogma: DNA transcribes to RNA, RNA translates to Protein –Both steps are regulated