A HIGH OBSERVED SUBSTITUTION RATE IN THE HUMAN MITOCHONDRIAL-DNA CONTROL REGION

The rate and pattern of sequence substitutions in the mitochondrial DN A (mtDNA) control region (CR) is of central importance to studies of h uman evolution and to forensic identity testing. Here, we report a dir ect measurement of the intergenerational substitution rate in the huma n 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 i n an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roug hly twenty-fold higher than estimates derived from phylogenetic analys es. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the d iscrepancy between very near-term and long-term apparent rates of sequ ence divergence. The data also indicate that extremely rapid segregati on of CR sequence variants between generations is common in humans, wi th a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.