L14-16 - 1 1 Biochemistry Sixth Edition Chapter 6:...

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Unformatted text preview: 1 1 Biochemistry Sixth Edition Chapter 6: Exploring Evolution and Bioinformatics Berg Tymoczko Stryer 2 Bioinformatics uses comparisons Can compare lots of things: 1.) DNA sequence There is lots of sequence available 2.) RNA sequence and structure (2 o mostly) There is lots of sequence and 2 o structure (computer predictable) Not as much 3 o structure 3.) Protein sequence and structure (3 o mostly) There is lots of sequence Increasing amounts of 3 o structure Expect structure to be very similar for same function; sequence may have drifted 3 Sequence of myoglobin: human ( red ), chimp ( blue ) Differ at only one amino acid Human and chimp DNA are 99% similar. Must be evolutionarily related. Evolutionary relationships: Manifest in protein sequence comparisons 2 4 Evolutionary relationships: Manifest in protein structural comparisons 1.) Proteins with same function from different species: orthologs 6.1) Homologs (orthologs and paralogs) are descended from a common ancestor 5 Evolutionary relationships: Manifest in protein structural comparisons 2.) Proteins with different function from same species: paralogs Human 6 Two classses of homologs: Paralogs and Orthologs DeFnitions homologs : two molecules that have descended by divergence from a common ancestor orthologs : homologs from different species with very similar or identical functions paralogs : homologs present within one species; often differ in detailed biochemical function Human 3 7 6.2) Sequence alignments are used to detect homology: 1.) Using Identities-only Are these two O 2-binding proteins similar (i.e . paralogous) ? Step 1: Align sequences Step 2: Judge the statistical signifcance oF the alignment 8 Step 1: Aligning sequences. (a) Slide sequences to maximize matches Start with C-terminus oF hemoglobin next to N-terminus oF myoglobin Slide hemoglobin across myoglobin one residue at a time Determine the 1 (or Few) alignments with greatest number oF matches 9 Step 1: Aligning sequences. (b) Allow gaps to accommodate the Few good matches Gap introduction is physically reasonable: Deletions oF one protein or insertions oF another are likely to occur on the evolutionary timescase (millions to billions oF years depending on the relationship) Here there are 38 oF 147 residues match (26% identical); Is this signifcant??? 4 10 Step 2: Judge the statistical signifcance oF sequence homologies (a) Give alignment a score Scoring rules: give 10 points For an identity; -25 For a gap (We have a penalty For gaps to prevent us From arbitrarily making these) Here: 38 identities; 1 gap Score: 355 = (10x38) + 1(-25) 1,2 3 ....1,2 3 ....
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L14-16 - 1 1 Biochemistry Sixth Edition Chapter 6:...

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