1. CS273a A Zero-Knowledge Based Introduction to Biology Courtesy of George Asimenos

2. Biology From the greek word βίος = life Timeline: 1683 – discovery of bacteria 1858 – Darwin’s natural selection 1865 – Mendel’s laws 1953 – double helix suggested by Watson-Crick 1955 – discovery of DNA and RNA polymerase 1978 – sequencing of first genome (5kb virus) 1983 – invention of PCR 1990 – discovery of RNAi 2000 – human genome (draft)

3. Properties of Biology Still a lot to understand Experimental data… are non-discrete have errors Hard to model ∀ rule ∃ exception

4. The Cell © 1997-2005 Coriell Institute for Medical Research cell, nucleus, cytoplasm, mitochondrion

5. Building an Organism cell DNA Every cell has the same sequence of DNA Subsets of the DNA sequence determine the identity and function of different cells

6. From DNA To Organism ? Proteins do most of the work in biology, and are encoded by subsequences of DNA, known as genes.

7. How many? Cells in the human body: >10 14 (100 trillion)

8. Chromosomes histone, nucleosome, chromatin, chromosome, centromere, telomere H1DNA H2A, H2B, H3, H4 ~146bp telomere centromere nucleosome chromatin

9. How many? Chromosomes in a human cell: 46 (2x22 + X/Y)

10. Nucleotide O CC CC H H HH H H H COPO O-O- O to next nucleotide to previous nucleotide to base deoxyribose, nucleotide, base, A, C, G, T, purine, pyrimidine, 3’, 5’ 3’ 5’ Adenine (A) Cytosine (C) Guanine (G) Thymine (T) Let’s write “AGACC”! pyrimidines purines

11. “AGACC” (backbone)

12. “AGACC” (DNA) deoxyribonucleic acid (DNA) 5’ 3’

13. DNA is double stranded 3’ 5’ 3’ DNA is always written 5’ to 3’ AGACC or GGTCT strand, reverse complement

14. RNA O CC CC H OH HH H H H COPO O-O- O to next ribonucleotide to previous ribonucleotide to base ribose, ribonucleotide, U 3’ 5’ Adenine (A) Cytosine (C) Guanine (G) Uracil (U) pyrimidines purines

15. How many? Nucleotides in the human genome: ~ 3 billion

16. Genes & Proteins 3’ 5’ 3’ TAGGATCGACTATATGGGATTACAAAGCATTTAGGGA...TCACCCTCTCTAGACTAGCATCTATATAAAACAGAA ATCCTAGCTGATATACCCTAATGTTTCGTAAATCCCT...AGTGGGAGAGATCTGATCGTAGATATATTTTGTCTT AUGGGAUUACAAAGCAUUUAGGGA...UCACCCUCUCUAGACUAGCAUCUAUAUAA (transcription) (translation) Single-stranded RNA protein Double-stranded DNA gene, transcription, translation, protein

17. How many? Genes in the human genome: ~ 20,000 – 25,000

18. Gene Transcription promoter 3’ 5’ 3’ G A T T A C A... C T A A T G T...

19. Gene Transcription transcription factor, binding site, RNA polymerase 3’ 5’ 3’ Transcription factors recognize transcription factor binding sites and bind to them, forming a complex. RNA polymerase binds the complex. G A T T A C A... C T A A T G T...

20. Gene Transcription 3’ 5’ 3’ The two strands are separated G A T T A C A... C T A A T G T...

21. Gene Transcription 3’ 5’ 3’ An RNA copy of the 5’ → 3’ sequence is created from the 3’ → 5’ template G A T T A C A... C T A A T G T... G A U U A C A

22. Gene Transcription 3’ 5’ 3’ G A U U A C A... G A T T A C A... C T A A T G T... pre-mRNA5’3’

23. RNA Processing 5’ cap, polyadenylation, exon, intron, splicing, UTR, mRNA 5’ cap poly(A) tail intron exon mRNA 5’ UTR3’ UTR

24. Gene Structure 5’3’ promoter 5’ UTR exons3’ UTR introns coding non-coding

25. How many? Exons per gene: ~ 8 on average (max: 148) Nucleotides per exon: 170 on average (max: 12k) Nucleotides per intron: 5,500 on average (max: 500k) Nucleotides per gene: 45k on average (max: 2,2M)

26. Amino acid amino acid C O N H C H HOH R There are 20 standard amino acids Alanine Arginine Asparagine Aspartate Cysteine Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine

27. Proteins C O N H C H R to previous aato next aa N-terminus HOH C-terminus N-terminus, C-terminus

28. Translation The ribosome synthesizes a protein by reading the mRNA in triplets (codons). Each codon is translated to an amino acid. ribosome, codon mRNA P siteA site

29. The Genetic Code

30. Translation 5’... A U U A U G G C C U G G A C U U G A... 3’ UTR Met Start Codon AlaTrpThr Stop Codon

31. Translation 5’... A U U A U G G C C U G G A C U U G A... 3’

32. Translation MetAla 5’... A U U A U G G C C U G G A C U U G A... 3’ Trp

33. Errors? What if the transcription / translation machinery makes mistakes? What is the effect of mutations in coding regions? mutation

34. Reading Frames reading frame G C U U G U U U A C G A A U U A G

35. Synonymous Mutation G C U U G U U U A C G A A U U A G Ala Cys Leu Arg Ile G C U U G U U U A C G A A U U A G synonymous (silent) mutation, fourfold site G G C U U G U U U G C G A A U U A G Ala Cys Leu Arg Ile

36. Missense Mutation G C U U G U U U A C G A A U U A G Ala Cys Leu Arg Ile G C U U G U U U A C G A A U U A G missense mutation G G C U U G G U U A C G A A U U A G Ala Trp Leu Arg Ile

37. Nonsense Mutation G C U U G U U U A C G A A U U A G Ala Cys Leu Arg Ile G C U U G U U U A C G A A U U A G nonsense mutation A G C U U G A U U A C G A A U U A G Ala STOP

38. Frameshift G C U U G U U U A C G A A U U A G Ala Cys Leu Arg Ile G C U U G U U U A C G A A U U A G frameshift G C U U G U U A C G A A U U A G Ala Cys Tyr Glu Leu

39. Gene Expression Regulation When should each gene be expressed? Regulate gene expression Examples: Make more of gene A when substance X is present Stop making gene B once you have enough Make genes C 1, C 2, C 3 simultaneously regulation

40. Regulatory Mechanisms enhancer, silencer Transcription Factor Specificity: Enhancer: Silencer:

41. The end?