title: Evolution of an Enzyme from a Noncatalytic Nucleic Acid Sequence.
abstract: The mechanism by which enzymes arose from both abiotic and biological worlds remains an unsolved natural mystery. We postulate that an enzyme can emerge from any sequence of any functional polymer under permissive evolutionary conditions. To support this premise, we have arbitrarily chosen a 50-nucleotide DNA fragment encoding for the Bos taurus (cattle) albumin mRNA and subjected it to test-tube evolution to derive a catalytic DNA (DNAzyme) with RNA-cleavage activity. After only a few weeks, a DNAzyme with significant catalytic activity has surfaced. Sequence comparison reveals that seven nucleotides are responsible for the conversion of the noncatalytic sequence into the enzyme. Deep sequencing analysis of DNA pools along the evolution trajectory has identified individual mutations as the progressive drivers of the molecular evolution. Our findings demonstrate that an enzyme can indeed arise from a sequence of a functional polymer via permissive molecular evolution, a mechanism that may have been exploited by nature for the creation of the enormous repertoire of enzymes in the biological world today.
authors.affiliation: 1] Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada [2] Origins Institute, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Gysbers
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.
authors.forename: Kha
authors.initials: K
authors.lastname: Tram
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Gu
authors.affiliation: 1] Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada [2] Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada [3] Origins Institute, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.
authors.forename: Yingfu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002417:Cattle; D021881:DNA, Catalytic / Q000737:chemistry / Q000235:genetics; D004798:Enzymes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D057166:High-Throughput Screening Assays; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics / Q000378:metabolism
chemical_list: D021881:DNA, Catalytic; D004798:Enzymes; D012313:RNA