title: A high observed substitution rate in the human mitochondrial DNA control region.
abstract: The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.
authors.affiliation: Armed Forces DNA Identification Laboratory, Armed Forces Institute of Pathology, Rockville, Maryland 20850, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Parsons
authors.forename: D S
authors.initials: DS
authors.lastname: Muniec
authors.forename: K
authors.initials: K
authors.lastname: Sullivan
authors.forename: N
authors.initials: N
authors.lastname: Woodyatt
authors.forename: R
authors.initials: R
authors.lastname: Alliston-Greiner
authors.forename: M R
authors.initials: MR
authors.lastname: Wilson
authors.forename: D L
authors.initials: DL
authors.lastname: Berry
authors.forename: K A
authors.initials: KA
authors.lastname: Holland
authors.forename: V W
authors.initials: VW
authors.lastname: Weedn
authors.forename: P
authors.initials: P
authors.lastname: Gill
authors.forename: M M
authors.initials: MM
authors.lastname: Holland
mesh_terms: D000818:Animals; D001483:Base Sequence; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D008297:Male; D016296:Mutagenesis; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial