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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 What Did this Table First Look Like? Is not a “frozen accident” There must have been earlier version I.e., this code must have evolved Hypothesis Earliest proteins evolved under an older version of the genetic code Current homologues to those proteins can be used to reconstruct these proteins Ancestral Sequence: S P K A N E Modern Descendents: S T S S P P P P R K K R V A V A N Q N N D E E E What Might Show The Evolution? Difference in amino acid composition between ANCESTRAL and DESCENDENT proteins We must find the earliest proteins from their modern descendents We must construct the ancestral sequences from their modern descendents Finding the Earliest Proteins bcd acd Eubacteria acdf E. coli Last Universal Ancestor cdhij Archaea Eukaryotes acde bcdg cdhijkl cdhijmn H. pylori A. pyrnix A. thaliana S. cerivisae cdhijmpq H. sapiens Reconstructed cd 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 Yeast Arabadopsis Human E. Coli Alanyl-tRNA synthetase Glycine hydroxymethyl transferase Seryl-tRNA synthetase Transcription antiterminator Chaperonin GroEL RecA/RadA recombinase … Reconstructing the Earliest Proteins Align all hits using CLUSTALW 1.74 Infer ancestral sequences using families of proteins. Modern Descendents: S T S S P P P P R K K R V A V A N Q N N D E E E Ancestral Sequence? S P K ? N E 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) Count Descendant Composition Obtain amino acid frequencies in families Compare with estimated ancestral composition Alanine: Alanine: Cysteine: Cysteine: Aspartate: Aspartate: Glutamate: Glutamate: Phenylalanine: Phenylalanine: Glycine: Glycine: Histidine: Histidine: Look for Significant Differences Changes imply changes in genetic code Relative changes also imply the sequence of changes Alanine: Alanine: Cysteine: Cysteine: Aspartate: Aspartate: Glutamate: Glutamate: Phenylalanine: Phenylalanine: Glycine: Glycine: Histidine: Histidine: 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