Ramos Amanda, Santos Cristina, Mateiu Ligia, Gonzalez Maria del Mar, Alvarez Luis, Azevedo Luisa, Amorim António, Aluja Maria Pilar
Unitat d'Antropologia Biològica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.
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.
确定人类线粒体异质性水平在多个领域至关重要。尽管如此，目前专注于这个问题的已发表作品很少。为了增加对线粒体DNA（mtDNA）异质性的了解，这项工作的主要目标是研究人类mtDNA基因组中异质性的频率和突变谱。为了解决这个问题，使用了一组九个引物对，这些引物对旨在避免共扩增线粒体起源的核DNA（nDNA）序列（NUMTs），以扩增101个人的线粒体基因组。所分析的个体代表了一个性别和mtDNA单倍群分布均衡的集合，类似于西欧人群。结果表明，异质个体的频率超过61%。点异质性的频率为28.7%，在整个mtDNA中广泛分布。此外，检测到异质性中有过量的转换，这表明遗传漂变和/或选择可能在群体水平上起作用以降低其频率。事实上，高度稳定位置的异质性可能对线粒体的活力有更大影响，这表明纯化选择必须在起作用以防止它们在个体中固定。本研究分析了健康人群中异质性的频率，对检测到的变化进行了进化分析，并在医学、进化和法医领域提供了具有重要意义的新视角。
