title: Primitive genetic polymers.
abstract: Since the structure of DNA was elucidated more than 50 years ago, Watson-Crick base pairing has been widely speculated to be the likely mode of both information storage and transfer in the earliest genetic polymers. The discovery of catalytic RNA molecules subsequently provided support for the hypothesis that RNA was perhaps even the first polymer of life. However, the de novo synthesis of RNA using only plausible prebiotic chemistry has proven difficult, to say the least. Experimental investigations, made possible by the application of synthetic and physical organic chemistry, have now provided evidence that the nucleobases (A, G, C, and T/U), the trifunctional moiety ([deoxy]ribose), and the linkage chemistry (phosphate esters) of contemporary nucleic acids may be optimally suited for their present roles-a situation that suggests refinement by evolution. Here, we consider studies of variations in these three distinct components of nucleic acids with regard to the question: Is RNA, as is generally acknowledged of DNA, the product of evolution? If so, what chemical and structural features might have been more likely and advantageous for a proto-RNA?
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Engelhart
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Hud
mesh_terms: D019418:Evolution, Chemical; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry*; D000069497:Origin of Life; D058105:Polymerization; D012313:RNA / Q000737:chemistry*
chemical_list: D009696:Nucleic Acids; D012313:RNA
references.citation: Nature. 2009 May 14;459(7244):239-42
references.pmid: 19444213
references.citation: Chem Commun (Camb). 2009 Feb 14;(6):647-9
references.pmid: 19322409
references.citation: Chem Commun (Camb). 2006 Jun 14;(22):2344-6
references.pmid: 16733574
references.citation: J Am Chem Soc. 2005 Jan 12;127(1):74-5
references.pmid: 15631455
references.citation: Biochemistry. 1977 Oct 18;16(21):4647-50
references.pmid: 911780
references.citation: Science. 1994 Aug 5;265(5173):777-80
references.pmid: 7519361
references.citation: Orig Life Evol Biosph. 2004 Jun;34(3):277-306
references.pmid: 15068036
references.citation: J Am Chem Soc. 2004 Aug 11;126(31):9578-83
references.pmid: 15291561
references.citation: Nature. 1993 Oct 7;365(6446):566-8
references.pmid: 7692304
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14598-603
references.pmid: 17785419
references.citation: J Am Chem Soc. 2009 Oct 21;131(41):14932-7
references.pmid: 19824732
references.citation: Cell. 1983 Dec;35(3 Pt 2):849-57
references.pmid: 6197186
references.citation: Orig Life Evol Biosph. 2000 Oct;30(5):405-10
references.pmid: 11002886
references.citation: Nature. 1990 Jan 4;343(6253):33-7
references.pmid: 1688644
references.citation: Angew Chem Int Ed Engl. 2007;46(14):2470-7
references.pmid: 17111452
references.citation: Angew Chem Int Ed Engl. 2009;48(5):960-3
references.pmid: 19130516
references.citation: J Mol Evol. 1992 Jul;35(1):1-6
references.pmid: 11536502
references.citation: Nature. 1994 May 19;369(6477):221-4
references.pmid: 8183342
references.citation: Proc Natl Acad Sci U S A. 1976 Apr;73(4):1149-53
references.pmid: 1063396
references.citation: J Am Chem Soc. 2008 Oct 8;130(40):13264-73
references.pmid: 18781753
references.citation: Int J Biol Macromol. 1995 Oct;17(5):239-46
references.pmid: 8580087
references.citation: Nature. 2000 Sep 21;407(6802):327-39
references.pmid: 11014182
references.citation: Angew Chem Int Ed Engl. 2007;46(14):2478-84
references.pmid: 17111453
references.citation: Science. 2000 Nov 17;290(5495):1306-7
references.pmid: 11185405
references.citation: Chem Biol. 1997 Apr;4(4):309-20
references.pmid: 9195870
references.citation: Curr Opin Chem Biol. 2004 Dec;8(6):672-89
references.pmid: 15556414
references.citation: J Theor Biol. 2000 Aug 21;205(4):543-62
references.pmid: 10931751
references.citation: Angew Chem Int Ed Engl. 2004 Apr 2;43(15):2004-8
references.pmid: 15065286
references.citation: Eur J Biochem. 2003 Apr;270(8):1628-44
references.pmid: 12694176
references.citation: Cold Spring Harb Perspect Biol. 2010 Apr;2(4):a005439
references.pmid: 20452951
references.citation: J Am Chem Soc. 2009 Feb 18;131(6):2119-21
references.pmid: 19166350
references.citation: J Mol Evol. 1995 Dec;41(6):693-702
references.pmid: 11536719
references.citation: J Am Chem Soc. 2009 Oct 14;131(40):14560-70
references.pmid: 19757789
references.citation: Chem Biodivers. 2007 Apr;4(4):694-720
references.pmid: 17443884
references.citation: J Mol Evol. 1972;1(3):249-57
references.pmid: 4681226
references.citation: Carbohydr Res. 2000 Nov 3;329(2):359-65
references.pmid: 11117319
references.citation: Chembiochem. 2003 Jun 6;4(6):514-21
references.pmid: 12794862
references.citation: Chemistry. 2006 Nov 15;12(33):8581-8
references.pmid: 16969774
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5938-43
references.pmid: 15840720
references.citation: J Am Chem Soc. 1965 Nov 20;87(22):5241-7
references.pmid: 5844818
references.citation: Orig Life Evol Biosph. 2006 Aug;36(4):343-61
references.pmid: 16915351
references.citation: Nat Rev Mol Cell Biol. 2004 Jun;5(6):451-63
references.pmid: 15173824
references.citation: J Am Chem Soc. 2006 Aug 23;128(33):10847-56
references.pmid: 16910680
references.citation: Z Naturforsch C Biosci. 1976 Jul-Aug;31(7-8):361-70
references.pmid: 8892
references.citation: Nature. 2008 Jul 3;454(7200):122-5
references.pmid: 18528332
references.citation: J Mol Biol. 1968 Dec;38(3):367-79
references.pmid: 4887876
references.citation: Nature. 2008 Feb 21;451(7181):977-80
references.pmid: 18288191
references.citation: Nucleic Acids Symp Ser. 2000;(44):217-8
references.pmid: 12903346
references.citation: Orig Life Evol Biosph. 2005 Feb;35(1):1-10
references.pmid: 15889646
references.citation: Antisense Nucleic Acid Drug Dev. 1997 Jun;7(3):187-95
references.pmid: 9212909
references.citation: Angew Chem Int Ed Engl. 2006 Sep 18;45(37):6176-9
references.pmid: 16917794
references.citation: J Mol Evol. 1994;38:549-57
references.pmid: 11539446
references.citation: Biochemistry. 1981 Mar 31;20(7):1874-80
references.pmid: 7013804
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Oct 29;361(1474):1743-9; discussion 1749
references.pmid: 17008215
references.citation: J Am Chem Soc. 2009 Nov 11;131(44):16088-95
references.pmid: 19839590
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14628-31
references.pmid: 12409606
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3868-71
references.pmid: 10760258
references.citation: Science. 2009 Jul 3;325(5936):73-7
references.pmid: 19520909
references.citation: J Am Chem Soc. 2008 Jan 16;130(2):412-3
references.pmid: 18095688
references.citation: Chembiochem. 2007 Mar 26;8(5):537-45
references.pmid: 17300110
references.citation: J Biol Chem. 2007 Jun 8;282(23):16729-35
references.pmid: 17412692
references.citation: Nucleic Acids Res. 1991 Jun 11;19(11):2979-86
references.pmid: 1711677
references.citation: J Mol Biol. 1962 Jun;4:500-17
references.pmid: 13885894
references.citation: Acc Chem Res. 2004 Oct;37(10):784-97
references.pmid: 15491125
references.citation: Orig Life Evol Biosph. 2001 Feb-Apr;31(1-2):71-86
references.pmid: 11296525
references.citation: Angew Chem Int Ed Engl. 2001 Jun 18;40(12):2249-2251
references.pmid: 11433484
references.citation: Nucleic Acids Res. 1985 Apr 11;13(7):2469-84
references.pmid: 4000962
references.citation: Chem Biol. 2007 May;14(5):525-31
references.pmid: 17524983
references.citation: J Am Chem Soc. 2009 Aug 19;131(32):11347-9
references.pmid: 19722647
references.citation: Chem Biodivers. 2007 Apr;4(4):768-83
references.pmid: 17443888
references.citation: J Am Chem Soc. 2007 Aug 8;129(31):9556-7
references.pmid: 17629276
references.citation: Nucleic Acids Res. 2006 Jan 31;34(2):564-74
references.pmid: 16449200
references.citation: Chembiochem. 2003 Jun 6;4(6):504-7
references.pmid: 12794860
references.citation: Nucleic Acids Res. 1987 Feb 25;15(4):1699-715
references.pmid: 3822836
references.citation: J Mol Biol. 1968 Dec;38(3):381-93
references.pmid: 5718557
references.citation: Acc Chem Res. 2006 Apr;39(4):231-7
references.pmid: 16618090
references.citation: Science. 2000 Aug 11;289(5481):905-20
references.pmid: 10937989
references.citation: Orig Life Evol Biosph. 2008 Feb;38(1):57-74
references.pmid: 18008180
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):853-8
references.pmid: 18195373
references.citation: Nature. 1961 Sep 16;191:1193-4
references.pmid: 13731264
references.citation: Proc Natl Acad Sci U S A. 1987 Jul;84(13):4398-402
references.pmid: 2440020
references.citation: Structure. 2003 Dec;11(12):1485-98
references.pmid: 14656433
references.citation: Angew Chem Int Ed Engl. 2004 Mar 26;43(14):1886-8
references.pmid: 15054804
references.citation: Science. 1966 Jul 1;153(3731):72-3
references.pmid: 5938419
references.citation: Naturwissenschaften. 2006 May;93(5):228-31
references.pmid: 16552527
references.citation: Curr Opin Chem Biol. 2004 Dec;8(6):654-9
references.pmid: 15556411
references.citation: J Am Chem Soc. 2002 Feb 6;124(5):746-7
references.pmid: 11817938
references.citation: Acc Chem Res. 2007 Feb;40(2):141-50
references.pmid: 17309194
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1470-5
references.pmid: 20080693
references.citation: J Mol Biol. 1970 Feb 14;47(3):531-43
references.pmid: 5418170
references.citation: Cell. 1982 Nov;31(1):147-57
references.pmid: 6297745
references.citation: Science. 1999 Jun 25;284(5423):2118-24
references.pmid: 10381870
references.citation: Orig Life Evol Biosph. 2001 Feb-Apr;31(1-2):87-102
references.pmid: 11296526
references.citation: Orig Life Evol Biosph. 2006 Feb;36(1):39-63
references.pmid: 16372197
references.citation: Science. 2000 Nov 17;290(5495):1347-51
references.pmid: 11082060
references.citation: J Am Chem Soc. 2004 Jan 14;126(1):40-1
references.pmid: 14709049
references.citation: Trends Biochem Sci. 1998 Dec;23(12):491-5
references.pmid: 9868373
references.citation: Chem Asian J. 2008 Jan 4;3(1):134-9
references.pmid: 18095296
references.citation: Chembiochem. 2008 Nov 24;9(17):2779-83
references.pmid: 18985646
references.citation: J Am Chem Soc. 2002 Nov 20;124(46):13716-21
references.pmid: 12431101
references.citation: Science. 2004 Jan 9;303(5655):196
references.pmid: 14716004
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5288-93
references.pmid: 20212163
references.citation: Science. 1983 Feb 18;219(4586):859-62
references.pmid: 6186026
references.citation: PLoS Biol. 2008 Jan;6(1):e18
references.pmid: 18215113
references.citation: Nat Struct Biol. 1997 Feb;4(2):98-101
references.pmid: 9033585
references.citation: Crit Rev Biochem Mol Biol. 2004 Mar-Apr;39(2):99-123
references.pmid: 15217990
references.citation: Chembiochem. 2006 Jun;7(6):951-6
references.pmid: 16642527
references.citation: Biochemistry. 1997 Jan 14;36(2):399-411
references.pmid: 9003193
references.citation: Science. 1987 Mar 6;235(4793):1173-8
references.pmid: 2434996
references.citation: Cold Spring Harb Symp Quant Biol. 1987;52:41-51
references.pmid: 2456883
references.citation: J Biomol Struct Dyn. 1999 Jun;16(6):1177-88
references.pmid: 10447202
references.citation: J Mol Biol. 1972 Jun 14;67(1):25-33
references.pmid: 4339529