title: Polymerase Interactions with Wobble Mismatches in Synthetic Genetic Systems and Their Evolutionary Implications.
abstract: In addition to completing the Watson-Crick nucleobase matching "concept" (big pairs with small, hydrogen bond donors pair with hydrogen bond acceptors), artificially expanded genetic information systems (AEGIS) also challenge DNA polymerases with a complete set of mismatches, including wobble mismatches. Here, we explore wobble mismatches with AEGIS with DNA polymerase 1 from Escherichia coli. Remarkably, we find that the polymerase tolerates an AEGIS:standard wobble that has the same geometry as the G:T wobble that polymerases have evolved to exclude but excludes a wobble geometry that polymerases have never encountered in natural history. These results suggest certain limits to "structural analogy" and "evolutionary guidance" as tools to help synthetic biologists expand DNA alphabets.
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Winiger
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC, 13709 Progress Blvd., Box 17, Alachua, Florida 32615, United States.
authors.forename: Myong-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC, 13709 Progress Blvd., Box 17, Alachua, Florida 32615, United States.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hoshika
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC, 13709 Progress Blvd., Box 17, Alachua, Florida 32615, United States.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Shaw
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC, 13709 Progress Blvd., Box 17, Alachua, Florida 32615, United States.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Moses
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Department of Chemistry, University of Florida , Gainesville, Florida 32611, United States.
authors.forename: Mariko F
authors.initials: MF
authors.lastname: Matsuura
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.
authors.forename: Dietlind L
authors.initials: DL
authors.lastname: Gerloff
authors.affiliation: Foundation for Applied Molecular Evolution (FfAME), 13709 Progress Blvd., Box 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC, 13709 Progress Blvd., Box 17, Alachua, Florida 32615, United States.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Benner
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004256:DNA Polymerase I / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D019143:Evolution, Molecular; D011485:Protein Binding
chemical_list: D004247:DNA; D004256:DNA Polymerase I