Frequency and pattern of heteroplasmy in the complete human mitochondrial genome

PLoS One. 2013 Oct 2;8(10):e74636. doi: 10.1371/journal.pone.0074636. eCollection 2013.


Determining the levels of human mitochondrial heteroplasmy is of utmost importance in several fields. In spite of this, there are currently few published works that have focused on this issue. In order to increase the knowledge of mitochondrial DNA (mtDNA) heteroplasmy, the main goal of this work is to investigate the frequency and the mutational spectrum of heteroplasmy in the human mtDNA genome. To address this, a set of nine primer pairs designed to avoid co-amplification of nuclear DNA (nDNA) sequences of mitochondrial origin (NUMTs) was used to amplify the mitochondrial genome in 101 individuals. The analysed individuals represent a collection with a balanced representation of genders and mtDNA haplogroup distribution, similar to that of a Western European population. The results show that the frequency of heteroplasmic individuals exceeds 61%. The frequency of point heteroplasmy is 28.7%, with a widespread distribution across the entire mtDNA. In addition, an excess of transitions in heteroplasmy were detected, suggesting that genetic drift and/or selection may be acting to reduce its frequency at population level. In fact, heteroplasmy at highly stable positions might have a greater impact on the viability of mitochondria, suggesting that purifying selection must be operating to prevent their fixation within individuals. This study analyses the frequency of heteroplasmy in a healthy population, carrying out an evolutionary analysis of the detected changes and providing a new perspective with important consequences in medical, evolutionary and forensic fields.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Genome, Mitochondrial / genetics*
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation


  • DNA, Mitochondrial

Grant support

This work was supported by MEC (projects: CGL2009-08205; CGL2006-07374; CGL2008-03408-E) and by Generalitat de Catalunya (Ref. 2009 SGR 566). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Education and Science, and is partially supported by Fundação para a Ciência e a Tecnologia. L. Alvarez is a FCT postdoctoral fellow (SFRH/BPD/65000/2009) at the IPATIMUP. L. Azevedo is supported by FCT through the program Ciencia2007 (Hiring of PhDs forthe SCTN - financed by POPH - QREN - Typology 4.2 - Promoting Scientific Employment, co-financed by MCTES national funding and The European Social Fund). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.