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

  title={A high observed substitution rate in the human mitochondrial DNA control region},
  author={Thomas J. Parsons and David Muniec and Kevin M. Sullivan and Nicola Woodyatt and R. Alliston-Greiner and Mark R. Wilson and Dianna L. Berry and Koren A. Holland and Victor W. Weedn and Peter Gill and Mitchell M. Holland},
  journal={Nature Genetics},
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… 
The mutation rate in the human mtDNA control region.
The present study sequenced the mtDNA control region in 272 individuals, who were related by a total of 705 mtDNA transmission events, from 26 large Icelandic pedigrees, and the estimated mutation rate is intermediate among those derived from pedigree-based studies.
Explaining the Imperfection of the Molecular Clock of Hominid Mitochondria
The findings imply the sluggishness of purifying selection in removing the slightly deleterious mutations from the human as well as the Neandertal and chimpanzee populations.
Mutation patterns of mtDNA: Empirical inferences for the coding region
The empirical estimation of mtDNA coding region mutation rate, calculated taking into account the sex of individuals carrying new mutations, the probability of intra-individual fixation of mutations present in heteroplasmy and, to the possible extent, the effect of selection, is similar to that obtained using phylogenetic approaches.
Characterizing the time dependency of human mitochondrial DNA mutation rate estimates.
It is proposed that demographic processes such as serial bottlenecks prior to the Holocene could explain the difference between rates estimated before and after 15,000 years ago, and human mtDNA estimates of dates of population and phylogenetic events should be adjusted.
MtDNA substitution rate and segregation of heteroplasmy in coding and noncoding regions
Abstract. The mitochondrial DNA (mtDNA) substitution rate and segregation of heteroplasmy were studied for the non-coding control region (D-loop) and 500 bp of the coding region between nucleotide
Phylogenetic and familial estimates of mitochondrial substitution rates: study of control region mutations in deep-rooting pedigrees.
The results reconcile the controversial rate estimates in the phylogenetic and familial studies; the fast sites prevail in the latter, whereas the slow and moderate sites dominate the phylogenetics-rate estimations.
Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J.
The results suggest that there are haplogroup-specific differences in the intensity of selection against particular regions of the mitochondrial genome, indicating that some mutations may be non-neutral within specific phylogenetic lineages but neutral within others.
Non-neutral sequence variation in human mitochondrial DNA: selection against deleterious mutations and haplogroup-related polymorphisms
The results are compatible with the assumption that selection has a marked role in human mtDNA evolution and that selective constraints may vary between populations, so that the pathogenic potential of a given mutation may depend markedly on the presence of other, interacting mutations.


Nonneutral mitochondrial DNA variation in humans and chimpanzees.
The sequenced NADH dehydrogenase subunit 3 (ND3) gene and published human RFLP data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases.
Age of the common ancestor of human mitochondrial DNA.
  • M. Nei
  • Biology
    Molecular biology and evolution
  • 1992
Vigilant et al. ( 199 1) concluded that the root of the phylogenetic tree for H mtDNAs is located at a sequence from African populations and that the age of the common H ancestral mtDNA is 166,000-249,000 years, but Hedges and Templeton challenged the first of these conclusions, showing that valid statistical tests do not support it.
How rapidly does the human mitochondrial genome evolve?
The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard
Intraspecific nucleotide sequence differences in the major noncoding region of human mitochondrial DNA.
The phylogenetic analysis indicates that diversity among the negroids is much larger than that among the caucasoids or the mongoloids, and can be separated into two distinct groups in the Japanese.
Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees.
A new mathematical method for estimating the number of transitional and transversional substitutions per site, as well as the total number of nucleotide substitutions, suggested that the transition/transversion ratio for the entire control region was approximately 15 and nearly the same for the two species.
Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs.
The shallow ancestry of human mtDNAs, together with the observation that the African sequence is the most diverged among humans, strongly supports the recent African origin of modern humans, Homo sapiens sapiens.
African populations and the evolution of human mitochondrial DNA.
The African origin hypothesis of human mtDNA evolution is supported by two statistical tests and two hypervariable segments of mtDNA were sequenced from 189 people of diverse geographic origin, including 121 native Africans.
Heteroplasmic point mutations in the human mtDNA control region.
The data from this study, together with unpublished data from other populations, are used to estimate the frequency of site heteroplasmy in normal human populations, and it is calculated that the rate of mutation and fixation in the first hypervariable segment of the human mtDNA control region is between 1.2 and 2.7 x 10(-6) per site per generation.
Evolutionary correlation between control region sequence and restriction polymorphisms in the mitochondrial genome of a large Senegalese Mandenka sample.
The deep coalescence times of sequences associated with the two most frequent restriction haplotypes confirm that the Niokolo Mandenka population has not passed through a recent bottleneck and that gene flow is maintained among West African populations despite ethnic differences.
Tempo and mode of synonymous substitutions in mitochondrial DNA of primates.
Heterogeneity of the mutation rate as well as of the constraint operating on the mtDNA-encoded proteins among different lineages of Hominoidea is suggested.