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Evolution of Amino Acid Frequencies in Proteins

Evolution of Amino Acid Frequencies in Proteins. Inferred Order of Introduction of Amino Acids into the Genetic Code. Extant Genetic Code. From: http://www.millerandlevine.com/Code-Table-Rect.html. Is not a “frozen accident” There must have been earlier version

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Evolution of Amino Acid Frequencies in Proteins

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  1. Evolution of Amino Acid Frequencies in Proteins Inferred Order of Introduction of Amino Acids into the Genetic Code

  2. Extant Genetic Code From: http://www.millerandlevine.com/Code-Table-Rect.html

  3. Is not a “frozen accident” There must have been earlier version I.e., this code must have evolved What Did this Table First Look Like?

  4. Earliest proteins evolved under an older version of the genetic code Current homologues to those proteins can be used to reconstruct these proteins Hypothesis Ancestral Sequence: S P K A N E Modern Descendents: S P R V N D T P K A Q E S P K V N E S P R A N E

  5. What Might Show The Evolution? • Difference in amino acid composition between ANCESTRAL and DESCENDENT proteins • We must find the earliest proteins fromtheir modern descendents • We must construct the ancestral sequences from their modern descendents

  6. Finding the Earliest Proteins Last Universal Ancestor c d b c d c d h i j a c d Reconstructed Eubacteria Archaea Eukaryotes a c d f a c d e b c d g c d h i j k l c d h i j m n c d h i j m p q E. coli H. pylori A. pyrnix A. thaliana S. cerivisae H. sapiens

  7. Finding the Earliest Proteins • Get protein families found in all branches of life • BLAST genomes vs. genomes • Find universal hits, i.e., proteins c and d Human Alanyl-tRNA synthetase Glycine hydroxymethyl transferase Seryl-tRNA synthetase Transcription antiterminator Chaperonin GroEL RecA/RadA recombinase … Yeast Arabadopsis E. Coli

  8. Reconstructing the Earliest Proteins • Align all hits using CLUSTALW 1.74 • Infer ancestral sequences using families of proteins. Modern Descendents: SPRVND TPKAQE SPKVNE SPRANE Ancestral Sequence? S P K ? N E

  9. Estimate Ancestral Composition • P(i|conserved) = P(i)*P(conserved|i)/P(conserved) • Get ancestral composition by rearranging equation and estimating terms • P(i)= ancestral composition = P(i|conserved)*P(conserved)/P(conserved|i)

  10. Count Descendant Composition • Obtain amino acid frequencies in families • Compare with estimated ancestral composition Alanine: Cysteine: Aspartate: Glutamate: Phenylalanine: Glycine: Histidine: Alanine: Cysteine: Aspartate: Glutamate: Phenylalanine: Glycine: Histidine:

  11. Changes imply changes in genetic code Relative changes also imply the sequence of changes Look for Significant Differences Alanine: Cysteine: Aspartate: Glutamate: Phenylalanine: Glycine: Histidine: Alanine: Cysteine: Aspartate: Glutamate: Phenylalanine: Glycine: Histidine:

  12. Conclusion • Structure promoting amino acids increased significantly over time • Phenylalanine, tryptophan, tyrosine, and cysteine • Early proteins may not have been enzymes • Significant changes in protein function over time

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