Download A common ancestor

Evolutionary and Genetic Origins
of Protein Sequences
Voet-Voet Chapter 7.3A-7.3B
Petsko-Ringe 4.0 to 4.3
A common ancestor
• All organisms are similar at the molecular
level
• Why?
• The higher the level of biochemical
organization, the greater the molecular
differences among species
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Phylogenetic tree
Similar sequence imply descent
from a common ancestor
• 1000 nucleotides (~333 aa)
– 41000 or 10600 different sequences
– ~1079 atoms in the universe
100 amino acids
- 20100 or 10130 different sequences
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Genes and proteins
• When are they homologues?
Partial homology
• % similarity vs % homology
Lys Arg
Asp Glu
Ser Thr
Tyr Phe Trp
Ala Val Leu Ile Met
Similarity vs Identity
• % sequence similarity
– S = [(Ls x 2)/ (La + Lb)] x 100
• % sequence identity
– I = [(Li x 2)/ (La + Lb)] x 100
– or I = Li/La%
3
E-values: probability that the two sequences will
have this degree of overall similarity by chance
single domain
multidomain
Functional assignment
from sequence comparison
none
fold
function
Enzymes
Non-enzymes
fold
What can be predicted from sequence comparison?
4
Detecting sequence homology
• Sequence alignment and comparison
– Curr. Op. Struc. Biol. 15, 254 (2005)
– Curr. Op. Struc. Biol. 15, 261 (2005)
– Curr. Op. Struc. Biol. 16, 368 (2006)
– Curr. Op. Struc. Biol. 16, 374 (2006)
Pairwise Sequence Alignment
• Methods
– Global alignment
• Closely related sequences
• Similar length
– Local alignment
• Divergent sequences
• Different length
• Identify domains or motifs
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Alignment Algorithms
• Dot matrix method
– Visually identify similar regions
http://bioweb.pasteur.fr/seqanal/interfaces/dotmatcher.html
• Dynamic programming method
– To find optimal alignments
Use scoring matrices (PAM, BLOSUM) and gap
penalties
• Word method
Database similarity searching (BLAST, FASTA)
Comparing homologous proteins
• Essential residues for its function
• Less significant
• Little specific function
6
Invariant
Conservatively substituted
Hypervariable
7
Phylogenetic tree of cytochrome c
Rates of
evolution
Unit of evolutionary period
8
Mutations rates are constant in time
Errors in replication
or
random chemical degradation
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