A high observed substitution rate in the human mitochondrial DNA control region

Thomas J. Parsons, David S. Muniec, Kevin Sullivan, Nicola Woodyatt, Rosemary Alliston-Greiner, Mark R. Wilson, Dianna L. Berry, Koren A. Holland, Victor W. Weedn, Peter Gill, Mitchell M. Holland

Research output: Contribution to journalArticlepeer-review

364 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)363-368
Number of pages6
JournalNature Genetics
Volume15
Issue number4
DOIs
StatePublished - Apr 1997

All Science Journal Classification (ASJC) codes

  • Genetics

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