Patterns of damage in genomic DNA sequences from a Neandertal.
High-throughput direct sequencing techniques have recently opened the possibility to sequence genomes from Pleistocene organisms. Here we analyze DNA sequences determined from a Neandertal, a mammoth, and a cave bear. We show that purines are overrepresented at positions adjacent to the breaks in the ancient DNA, suggesting that depurination has contributed to its degradation. We furthermore show that substitutions resulting from miscoding cytosine residues are vastly overrepresented in the DNA sequences and drastically clustered in the ends of the molecules, whereas other substitutions are rare. We present a model where the observed substitution patterns are used to estimate the rate of deamination of cytosine residues in single- and double-stranded portions of the DNA, the length of single-stranded ends, and the frequency of nicks. The results suggest that reliable genome sequences can be obtained from Pleistocene organisms.
Briggs
Adrian W
AW
Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany. briggs@eva.mpg.de
Stenzel
Udo
U
Johnson
Philip L F
PL
Green
Richard E
RE
Kelso
Janet
J
Prüfer
Kay
K
Meyer
Matthias
M
Krause
Johannes
J
Ronan
Michael T
MT
Lachmann
Michael
M
Pääbo
Svante
S
D017122:Bacteriophage T4 / Q000201:enzymology; D001483:Base Sequence; D003198:Computer Simulation; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000266:history; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003641:Deamination; D016678:Genome; D015698:Genomic Library; D049690:History, Ancient; D006801:Humans; D016013:Likelihood Functions; D008954:Models, Biological; D008969:Molecular Sequence Data; D010163:Paleontology / Q000379:methods*; D016133:Polymerase Chain Reaction; D012015:Reference Standards; D017422:Sequence Analysis, DNA; D013698:Templates, Genetic
D003596:Cytosine; D004247:DNA; D004259:DNA-Directed DNA Polymerase
Annu Rev Genet. 2004;38:645-79
15568989
Nat Rev Genet. 2001 May;2(5):353-9
11331901
Curr Biol. 2006 Aug 22;16(16):R630-2
16920607
Nucleic Acids Res. 2001 Dec 1;29(23):4793-9
11726688
Curr Biol. 2006 Jun 6;16(11):R400-2
16753548
PLoS Biol. 2004 Mar;2(3):E57
15024415
Biol Chem. 2006 Apr;387(4):373-9
16606334
Nature. 2005 Sep 15;437(7057):376-80
16056220
Proc Natl Acad Sci U S A. 1989 Mar;86(6):1939-43
2928314
Nucleic Acids Res. 1996 Apr 1;24(7):1304-7
8614634
Nucleic Acids Res. 2007;35(1):1-10
16920744
Biochemistry. 1972 Sep 12;11(19):3618-23
4559796
Science. 2005 Jul 22;309(5734):597-9
15933159
Curr Biol. 2006 Aug 22;16(16):R629-30
16920606
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1122-6
8430083
Curr Opin Genet Dev. 2006 Dec;16(6):545-52
17055251
Science. 2006 Jan 20;311(5759):392-4
16368896
Science. 2006 Nov 17;314(5802):1113-8
17110569
Mol Biol Evol. 2006 Sep;23(9):1801-7
16809622
Nat Genet. 2000 Oct;26(2):144-6
11017066
Mol Biol Evol. 2005 Oct;22(10):2040-7
15958782
Nucleic Acids Res. 2007;35(17):5717-28
17715147
Nature. 2001 Feb 15;409(6822):860-921
11237011
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13578-84
16938852
Mol Biol Evol. 2005 Apr;22(4):1077-81
15689531
Nature. 2000 Mar 30;404(6777):490-3
10761915
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13342-7
12232049
Cell. 1997 Jul 11;90(1):19-30
9230299
Nature. 2006 Nov 16;444(7117):330-6
17108958
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7085-90
15878988
Nature. 1993 Apr 22;362(6422):709-15
8469282