1. Today Building a genome –Nucleotides, GC content and isochores –Gene structure and expression; introns –Evolution of noncoding RNAs Evolution of transcription –Transcription & Translation –Recoding and RNA editing –Evolution of the genetic code

2. The four nucleotides of DNA

3. Watson & Crick actually got it wrong …

4. GC content versus optimal growth temperature Genome-wide Ribosomal RNAs

5. Environmental signature on GC content

6. Structure of human isochores

7. Lack of isochores in lizards

8. GC-content correlates with recombination rate

9. A B C { AAAAAA { Influences gene from afar…. D E F G GH { A._______________ B. _______________ C. _______________ D. _______________ E. _______________ F. _______________ G. _______________ H. _______________ I. _______________ I I Anatomy of a eukaryotic gene

10. Introns cleaved out by the spliceosome

11. Phylogenetic distribution of introns implies recent origin

12. Intron phase and size

13. Rotem Sorek et al. Genome Res. 2003; 13: 1631-1637 Figure 3 Human-mouse alignment of the KCND3 gene, corresponding to RefSeq NM_004980 (from VISTA browser, http://pipeline.lbl.gov/vistabrowser/) Intronic regions adjacent to exons are often conserved

14. 2005: Widespread transcription in the human genome revealed by microarray analysis

15. Fast forward 2010: Expression tracks known genes closely

16. Number of regulatory genes (R) vs. total number of genes (G) Circles - Bacteria; triangles - Archaea R = 0.00002G 2 Mycoplasma genitalium Bradyrhizobium japonicum

17. Does ‘noncoding DNA’ increase genomic complexity?

18. Was eukaryotic complexity released by noncoding RNAs?

19. MicroRNAs - a new class of small RNAs with big roles in development and evolution

20. Translational repression by microRNAs

21. microRNAs as cladistic characters

22. Explosive diversity of cichlid fish

23. Rapid evolution of microRNA targets – a link with speciation?

24. The ‘universal’ genetic code

26. Translation

27. Phe 12s rRNA Val 16s rRNA Leu Ile Gln Met Trp Ala Asn Cys Tyr COI Ser Asp COII Lys ATP8 ATP6 COIII Gly NADH3 Arg NADH4L NADH4 His Ser Leu NADH5 Cyt b Thr Control Region Pro NADH6 Glu noncoding Structure of vertebrate mitochondrial DNA (~17,000 bp) rRNA genes tRNA genes ATP synthase genes Cytochrome bc1 complex Cytochrome Oxidase NADH:Ubiquinone Oxidoreductase NADH1 NADH2

28. Four ways to change the coding of amino acids from RNA

29. Wobble rules in various organisms base modifications in tRNAs can increase decoding breadth

30. A code that minimizes polarity changes better than the universal code