Scoring :qt

2. FBW 20-10-2011 Wim Van Criekinge

6. Anno 2002 Anno 2003

7. Anno 2004

8. Anno 2005

9. Anno 2006

10. Anno 2007

11. Anno 2009

12. Anno 2010 Anno 2010

13. Anno 2011

15. Identity The extent to which two (nucleotide or amino acid) sequences are invariant. Homology Similarity attributed to descent from a common ancestor. Definitions RBP: 26 RV K ENFDKARFS GTW YA MA KKDPEGLFLQDNIV A EFS V DE T GQMSATAKGRVRL L NN W D- 84 + K ++ + + GTW ++ MA + L + A V T + + L + W + glycodelin: 23 QT K QDLELPKLA GTW HS MA MA-TNNISLMATLK A PLR V HI T SLLPTPEDNLEIV L HR W EN 81

16. Orthologous Homologous sequences in different species that arose from a common ancestral gene during speciation; may or may not be responsible for a similar function. Paralogous Homologous sequences within a single species that arose by gene duplication. Definitions

17. speciation duplication

18. fly GAKKVIISAP SAD.APM..F VCGVNLDAYK PDMKVVSNAS CTTNCLAPLA human GAKRVIISAP SAD.APM..F VMGVNHEKYD NSLKIISNAS CTTNCLAPLA plant GAKKVIISAP SAD.APM..F VVGVNEHTYQ PNMDIVSNAS CTTNCLAPLA bacterium GAKKVVMTGP SKDNTPM..F VKGANFDKY. AGQDIVSNAS CTTNCLAPLA yeast GAKKVVITAP SS.TAPM..F VMGVNEEKYT SDLKIVSNAS CTTNCLAPLA archaeon GADKVLISAP PKGDEPVKQL VYGVNHDEYD GE.DVVSNAS CTTNSITPVA fly KVINDNFEIV EGLMTTVHAT TATQKTVDGP SGKLWRDGRG AAQNIIPAST human KVIHDNFGIV EGLMTTVHAI TATQKTVDGP SGKLWRDGRG ALQNIIPAST plant KVVHEEFGIL EGLMTTVHAT TATQKTVDGP SMKDWRGGRG ASQNIIPSST bacterium KVINDNFGII EGLMTTVHAT TATQKTVDGP SHKDWRGGRG ASQNIIPSST yeast KVINDAFGIE EGLMTTVHSL TATQKTVDGP SHKDWRGGRT ASGNIIPSST archaeon KVLDEEFGIN AGQLTTVHAY TGSQNLMDGP NGKP.RRRRA AAENIIPTST fly GAAKAVGKVI PALNGKLTGM AFRVPTPNVS VVDLTVRLGK GASYDEIKAK human GAAKAVGKVI PELNGKLTGM AFRVPTANVS VVDLTCRLEK PAKYDDIKKV plant GAAKAVGKVL PELNGKLTGM AFRVPTSNVS VVDLTCRLEK GASYEDVKAA bacterium GAAKAVGKVL PELNGKLTGM AFRVPTPNVS VVDLTVRLEK AATYEQIKAA yeast GAAKAVGKVL PELQGKLTGM AFRVPTVDVS VVDLTVKLNK ETTYDEIKKV archaeon GAAQAATEVL PELEGKLDGM AIRVPVPNGS ITEFVVDLDD DVTESDVNAA Multiple sequence alignment of glyceraldehyde- 3-phsophate dehydrogenases

54. Other similarity scoring matrices might be constructed from any property of amino acids that can be quantified - partition coefficients between hydrophobic and hydrophilic phases - charge - molecular volume Unfortunately, …

56. Protein Eng. 1996 Jan;9(1):27-36.

65. Dayhoff’s PAM1 mutation probability matrix (Transition Matrix)

83. Dayhoff’s PAM1 mutation probability matrix (Transition Matrix)

85. PAM-Simulator

86. PAM-Simulator

91. 4 3 2 1 0 A brief history of time (BYA) Origin of life Origin of eukaryotes insects Fungi/animal Plant/animal Earliest fossils BYA

92. Margaret Dayhoff’s 34 protein superfamilies Protein PAMs per 100 million years Ig kappa chain 37 Kappa casein 33 Lactalbumin 27 Hemoglobin  12 Myoglobin 8.9 Insulin 4.4 Histone H4 0.10 Ubiquitin 0.00

96. BLOSUM ( BLO ck – SUM ) scoring DDNAAV DNAVDD NNVAVV Block = ungapped alignent Eg. Amino Acids D N V A a b c d e f 1 2 3 S = 3 sequences W = 6 aa N= (W*S*(S-1))/2 = 18 pairs

97. A. Observed pairs DDNAAV DNAVDD NNVAVV a b c d e f 1 2 3 D N A V D N A V 1 4 1 3 1 1 1 1 4 1 f f ij D N A V D N A V .056 .222 .056 .167 .056 .056 .056 .056 .222 .056 g ij /18 Relative frequency table Probability of obtaining a pair if randomly choosing pairs from block

98. B. Expected pairs A DDDDD NNNN AAAA VVVVV DDNAAV DNAVDD NNVAVV P i 5/18 4/18 4/18 5/18 P{Draw DN pair}= P{Draw D, then N or Draw M, then D} P{Draw DN pair}= P D P N + P N P D = 2 * (5/18)*(4/18) = .123 D N A V D N A V .077 .123 .154 .123 .049 .123 .099 .049 .123 .049 e ij Random rel. frequency table Probability of obtaining a pair of each amino acid drawn independently from block

105. Rat versus mouse RBP Rat versus bacterial lipocalin

114. Reduction of Dot Plot Noise Self alignment of ACCTGAGCTCACCTGAGTTA

116. Chromosome Y self comparison