Nothing in (computational) biology makes

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Nothing in (computational) biology makes sense
except in the light of evolution
after Theodosius Dobzhansky (1970)
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A brief history and some central principles
of evolutionary (computational) genomics
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J. Mol Biol 1982 Dec 25162(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...
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Growth of the number of completely sequenced
genomes
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Figure 1.2. The current state of annotation of
some genomes. The data were derived from the
original genome sequencing papers
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Nothing in (computational) biology makes sense
except in the light of evolution
after Theodosius Dobzhansky (1970)
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Homology common ancestry of genes or portions
thereof (a qualitative notion as opposed to
similarity)
Species 1
Species 3
Species 2
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Evolution by gene duplication, 1970
Gene duplication with subsequent diversification
- the principal path to innovation in evolution
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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
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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
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Gene loss
speciation
descendants
ancestor
Gene loss
Non-orthologous displacement two unrelated (or
distantly related) proteins for the same
essential function
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Figure 2.3. Structural alignment of goose
lysozyme (PDB code 153L), chicken egg white
lysozyme (3LZT) and lysozymes from E. coli
bacteriophages l (1AM7) and T4 (1L92).
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153L .GEKLC.VE.PAVIAGIISRESHAG..KVLK....NGWGD.
..R.......... 3LZT gLDNYRgYS.LGNWVCAAKFESNFN...
......tQATNR...N.......... 1AM7
.mvEIN.NQrKAFLDMLAWSEGTDngrQKTRnhgyDVIVGgelftdysdh
prkl 1L92 ..........MNIFEMLRIDEG...........lrlK
IYKdteG..........   153L ........GNGFGLMQVDKRSH
...............KP........QG..TWN 3LZT
.....tdgsTDYGILQINSRWWcndgrtpgsrnlcniPC........SAl
lSSD 1AM7 vtlnpklkSTGAGRYQLLSRWW...............
DayrkqlglkDF..SP. 1L92 ........YYTIG.IGHLLT....
.....kspslnaakseldkaigrntngvIT   153L
.GEVHITQGTTILINF.IKTIQK...KFPS.WTKD..QQLKGGISAYNAG
AGNVR 3LZT ITASVNCAKKIVSDG.N...................
.....GMNAWV....... 1AM7 ..KSQDAVALQQIKERgALPM...
........idR..GDIRQAIDRCSN....iw 1L92
.KDEAEKLFNQDVDAA.VRGILRnakLKPVyDSLDavRRAAIINMVFQMG
ETGVA   153L .SYARMDIGT....................THDDY
ANDVV....ARAQYYKQHGY 3LZT .....................
...........awRNRCK...gTDVQAWIRGCr 1AM7
.aslpGAGY...................gqfEHKA.DSLI....AKFKEA
Ggtvr 1L92 .gftnslrmlqqkrwdeaavnlaksrwynqTPNRAkr
vittfrtgtwDAYK....
 
Structure-based sequence alignment of goose
lysozyme (153L), chicken egg white lysozyme
(3LZT) and lysozymes from E. coli bacteriophages
l (1AM7) and T4 (1L92).
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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