1.  Shai Shen-Orr shenorr@stanford.edu

2.  Nothing in Biology Makes Sense Except in the Light of Evolution  Theodosius Dobzhansky 1973

3. Jeffrey Decoster, Stanford Medical Magazine, Summer 06 http://stanmed.stanford.edu/2006summer/ev olutionary-medicine.html

4.  Negative (purifying) selection – selective removal of rare alleles that are deleterious  Positive selection – selection due to added fitness to a particular allele  Balancing selection – Selection due to heterozygote or frequency dependent advantage

5. http://www.genomesonline.org/gold.cgi

9. Fitch et al. PNAS 1997

10. Bush et al. Science 1999

11. Sawyer et al. PNAS 2005

13. Kaiser et al. Science 2007

17. Arabidopsis thaliana 114.5 Mb genome (Sequenced 2000 ) Chlamydomonas reinhardtii 95 Mb genome (Sequenced 2004)

18. Li et al. Cell 2004

20. Ala et al. PLoS Comp Bio 2008

22. How similar is the Disease Gene Expression Profile of a human disease and its mouse model ?

23. Diseased Subjects Control subjects Subtract Disease gene expression signature Rank Normalize

24. MDX mouseWildtype ControlDMD patientsControl Disease gene expression signature Human Mouse Limit to Human – Mouse 1:1 orthologs

25. Human Disease gene expression signature Mouse Disease gene expression signature Spearman’s ρ = 0.28

26. Human Disease gene expression signature Mouse Disease gene expression signature Spearman’s ρ = 0.28 Spearman’s ρ Rank Correlation

27. Cross-species Mouse X Mouse Human X Human

28. Spearman’s ρ Rank Correlation Cross-species Mouse X Mouse Human X Human

29. Spearman’s ρ Rank Correlation Cross-species Mouse X Mouse Human X Human

30. Spearman’s ρ Rank Correlation Cross-species Mouse X Mouse Human X Human