1. Nothing in (computational) biology makes sense except in the light of evolution after Theodosius Dobzhansky (1970)

2. A brief history and some central principles of evolutionary (computational) genomics

11. J. Mol Biol 1982 Dec 25;162(4):729-73 Nucleotide sequence of bacteriophage lambda DNA. Sanger F, Coulson AR, Hong GF, Hill DF, Petersen GB. The DNA in its circular form contains 48,502 pairs of nucleotides. … Open reading frames were identified and, where possible, ascribed to genes by comparing with the previously determined genetic map. The reading frames for 46 genes were clearly identified… There are about 20 other unidentified reading frames that may code for proteins. … Protein sequence comparison or homology are not mentioned in this paper...

21. Growth of the number of completely sequenced genomes

30. Figure 1.2. The current state of annotation of some genomes. The data were derived from the original genome sequencing papers

31. Nothing in (computational) biology makes sense except in the light of evolution after Theodosius Dobzhansky (1970)

32. Species 1 Species 2 Species 3 Homology: common ancestry of genes or portions thereof (a qualitative notion as opposed to similarity)

33. Evolution by gene duplication, 1970 Gene duplication with subsequent diversification - the principal path to innovation in evolution

35. Number of proteins in COGs not in COGs The majority of the proteins in each prokaryote, but only ~1/3 of yeast proteins belong to COGs - ancient conserved families

36. MOST OF THE COGs ARE REPRESENTED ONLY IN A SMALL NUMBER OF CLADES MAJOR ROLE OF HORIZONTAL GENE TRANSFER AND CLADE-SPECIFIC GENE LOSS IN EVOLUTION

37. ancestor descendants speciation Gene loss Non-orthologous displacement: two unrelated (or distantly related) proteins for the same essential function Gene loss

38. Figure 2.3. Structural alignment of goose lysozyme (PDB code 153L), chicken egg white lysozyme (3LZT) and lysozymes from E. coli bacteriophages (1AM7) and T4 (1L92).

39. 153L.GEKLC.VE.PAVIAGIISRESHAG..KVLK....NGWGD...R.......... 3LZT gLDNYRgYS.LGNWVCAAKFESNFN.........tQATNR...N.......... 1AM7.mvEIN.NQrKAFLDMLAWSEGTDngrQKTRnhgyDVIVGgelftdysdhprkl 1L92..........MNIFEMLRIDEG...........lrlKIYKdteG.......... 153L........GNGFGLMQVDKRSH...............KP........QG..TWN 3LZT.....tdgsTDYGILQINSRWWcndgrtpgsrnlcniPC........SAllSSD 1AM7 vtlnpklkSTGAGRYQLLSRWW...............DayrkqlglkDF..SP. 1L92........YYTIG.IGHLLT.........kspslnaakseldkaigrntngvIT 153L.GEVHITQGTTILINF.IKTIQK...KFPS.WTKD..QQLKGGISAYNAGAGNVR 3LZT ITASVNCAKKIVSDG.N........................GMNAWV....... 1AM7..KSQDAVALQQIKERgALPM...........idR..GDIRQAIDRCSN....iw 1L92.KDEAEKLFNQDVDAA.VRGILRnakLKPVyDSLDavRRAAIINMVFQMGETGVA 153L.SYARMDIGT....................THDDYANDVV....ARAQYYKQHGY 3LZT................................awRNRCK...gTDVQAWIRGCr 1AM7.aslpGAGY...................gqfEHKA.DSLI....AKFKEAGgtvr 1L92.gftnslrmlqqkrwdeaavnlaksrwynqTPNRAkrvittfrtgtwDAYK.... Structure-based sequence alignment of goose lysozyme (153L), chicken egg white lysozyme (3LZT) and lysozymes from E. coli bacteriophages (1AM7) and T4 (1L92).

40. Only a small fraction of amino acid residues is directly involved in protein function (including enzymatic); the rest of the protein serves largely as structural scaffold Significant sequence conservation is evidence of homology Proteins with different structural folds can perform the same function - non-orthologous displacement Proteins (domains) with the same fold are most likely to be homologous Convergence does not produce significant sequence or structural similarity