TY - JOUR

T1 - Distribution patterns of postmortem damage in human mitochondrial DNA

AU - Gilbert, M Thomas P

AU - Willerslev, Eske

AU - Hansen, Anders J

AU - Barnes, Ian

AU - Rudbeck, Lars

AU - Lynnerup, Niels

AU - Cooper, Alan

N1 - Keywords: Animals; DNA Damage; DNA Glycosylases; DNA, Mitochondrial; Electron Transport Complex IV; Haplotypes; Humans; Mitochondria; Mitochondrial Proteins; Mutagenesis; N-Glycosyl Hydrolases; Polymerase Chain Reaction; Postmortem Changes; Species Specificity; Tooth; Uracil-DNA Glycosidase; Ursidae

PY - 2002

Y1 - 2002

N2 - The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region 1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage.

AB - The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region 1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage.

U2 - 10.1086/345378

DO - 10.1086/345378

M3 - Journal article

C2 - 12489041

VL - 72

SP - 32

EP - 47

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -