1. Biological background: Molecular Biology Class web site: http://statwww.epfl.ch/davison/teaching/Microarrays/ETHZ/ Statistics for Microarrays

2. Two types of organisms * * Every biological ‘rule’ has exceptions!

3. http://www.stg.brown.edu/webs/MendelWeb/MWtoc.html Mendelian Genetics

4. Human Chromosomes

5. Human Chromosome Banding Patterns

6. Chromosomes and DNA

7. Mitosis and Meiosis Compared

8. Nature (1953), 171:737 “We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.” DNA Structure Discovery

9. DNA A deoxyribonucleic acid or DNA molecule is a double-stranded linear polymer composed of four molecular subunits called nucleotides Each nucleotide comprises a phosphate group, a deoxyribose sugar, and one of four nitrogen bases: adenine (A), guanine (G), cytosine (C), or thymine (T) The two strands are held together by weak hydrogen bonds between complementary bases Base-pairing occurs according to the rule: G pairs with C, and A pairs with T

10. DNA A-type (140D) (low water content) DNA B-type (7BNA) (Watson-Crick form) DNA Z-type (2ZNA) (high salt concentration) Polymorphic DNA Tertiary Structures

11. Genes are linearly arranged along chromosomes

12. DNA Structure (overview)

13. A nucleotide is a phospate, a sugar, and a purine (A, G) or a pyramidine (T, C) base. The monomeric units of nucleic acids are called nucleotides. DNA Structure

14. Proteins Proteins: macromolecules composed of one or more chains of amino acids Amino acids: class of 20 different organic compounds containing a basic amino group (-NH 2 ) and an acidic carboxyl group (- COOH) The order of amino acids is determined by the base sequence of nucleotides in the gene coding for the protein Proteins function as enzymes, antibodies, structures, etc.

15. Amino acid codes

16. Primary Protein Structure

17. Multiple Levels of Protein Strucure (  Protein folding )

18. Tertiary Structure of Sperm whale myoglobin (1MBN)

19. (RT)

20. Nature (1953), 171:737 “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” DNA Replication

22. The DNA strand that is copied to form a new strand is called a template In the replication of a double-stranded or duplex DNA molecule, both original (parental) DNA strands are copied When copying is finished, the two new duplexes, each consisting of one of the original strands plus its copy, separate from each other (semiconservative replication)

23. Semiconservative Replication

24. DNA Replication, ctd Synthesis occurs in the chemical direction 5’  3’ Nucleic acid chains are assembled from 5’ triphosphates of deoxyribonucleosides (the triphosphates supply energy) DNA polymerases are enzymes that copy DNA DNA polymerases require a short preexisting DNA strand (primer) to begin chain growth. With a primer base-paired to the template strand, a DNA polymerase adds nucleotides to the free hydroxyl group at the 3’ end of the primer. DNA replication requires assembly of many proteins (at least 30) at a growing replication fork: helicases to unwind, primases to prime, ligases to ligate (join), topisomerases to remove supercoils, RNA polymerase, etc.

26. DNA Replication Fork

27. DNA is unwinding  DNA Synthesis

30. RNA RNA, or ribonucleic acid, is similar to DNA, but -- RNA is (usually) single-stranded -- the sugar is ribose rather than deoxyribose -- uracil (U) is used instead of thymine RNA is important for protein synthesis and other cell activities There are several classes of RNA molecules, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and other small RNAs

31. The Genetic Code DNA: sequence of four different nucleotides Protein: sequence of twenty different amino acids The correspondence between the four- letter DNA alphabet and the twenty- letter protein alphabet is specified by the genetic code, which relates nucleotide triplets, or codons, to amino acids

32. Standard Genetic Code

33. Variation of genetic codes T1: standard T2: vert mt T3: yeast mt T4: other mt T5: invert. mt T6: cil. etc nuc. T9: ech. mt T10: eup. nuc. T12:alt yeast nuc T13: asc. mt T14: flat. mt T15: bleph. nuc.

34. Protein Synthesis

35. Transcription Transcription is a complex process involving several steps and many proteins (enzymes) RNA polymerase synthesizes a single strand of RNA against the DNA template strand (anti- sense strand), adding nucleotides to the 3’ end of the RNA chain Initiation is regulated by transcription factors, including promoters, usually an initiator element and TATA box, usually lying just upstream (at the 5’ end) of the coding region 3’ end cleaved at AAUAAA, poly-A tail added

36. Exons and Introns Most of the genome consists of non-coding regions Some non-coding regions (centromeres and telomeres) may have specific chomosomal functions Other non-coding regions have regulatory purposes Non-coding, non-functional DNA often called junk DNA, but may have some effect on biological functions The terms exon and intron refer to coding and non-coding DNA, respectively

37. Intron Splicing

38. Translation The AUG start codon is recognized by methionyl-tRNA i Met Once the start codon has been identified, the ribosome incorporates amino acids into a polypeptide chain RNA is decoded by tRNA (transfer RNA) molecules, which each transport specific amino acids to the growing chain Translation ends when a stop codon (UAA, UAG, UGA) is reached

39. Translation Illustrated

40. From Primary Transcript to Protein

41. Alternative Splicing (of Exons) How is it possible that there are millions of human antibodies when there are only about 30,000 genes? Alternative splicing refers to the different ways the exons of a gene may be combined, producing different forms of proteins within the same gene-coding region Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in higher eukaryotes

43. Acknowledgements http://www.accessexcellence.org/AB/GG http://www.oup.co.uk/best.textbooks/bioch emistry/genesviihttp://www.oup.co.uk/best.textbooks/bioch emistry/genesvii Sandrine Dudoit, UC Berkeley Biostatistics Yee Hwa Yang, UC Berkeley Statistics Terry Speed, UC Berkeley Statistics and WEHI, Melbourne, Australia