Appendix e-1. Mitochondrial DNA and Haplogroups.
Mitochondria contain in their matrix hundreds to thousands copies of a small (~16.6 Kb), maternally inherited, circular, non-recombining molecule of DNA (mtDNA), which comprises 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes code for protein subunits, all parts of the multimeric enzymatic complexes involved in the oxidative phosphorylation (OXPHOS), of which the remaining subunits are produced by nuclear DNA, transported to, and assembled within, the mitochondria. The non-coding region of mtDNA has an extremely high mutation rate and is therefore highly polymorphic. A specific collection of mtDNA mutations is termed haplotype; haplotypes sharing some mutations derived by the same ancestor mtDNA form a haplogroup[1]. Ten haplogroups (H, I, J, K, M, T, U, V, W and X) account for about 99% of those of the Euro-Asian population, but haplogroup H characterizes more than 40% of the whole European population[2], although it is the most recent haplogroup appeared in Europe, (at the pick of the last Ice Age) and the fastest to spread and evolve in its, at least, 15 subhaplogroups[3]. Interestingly, different haplogroups give the impression to exhibit different OXPHOS performances. Even if these data are still disputed (see in article’s discussion section), haplogroup H apparently differs from others, since it seems the more active one[4]. Moreover, a number of neurodegenerative conditions, such as Parkinson’s disease, Alzheimer’s dementia, or Leber’s hereditary optic neuropathy, but also male infertility or human longevity have been associated with specific mtDNA haplogroups, though most often in single studies (see review by Herrnstadt et Howell[5]).
References
1. Torroni A, Schurr TG, Cabell MF, et al. Asian affinities and continental radiation of the four founding Native American mtDNAs. American Journal of Medical Genetics. 1993;53:563-590.
2. Torroni A, Huoponen K, Francalacci P, et al. Classification of European mtDNAs from an analysis of three European populations. Genetics. 1996;144:1835-1850.
3. Achilli A, Rengo C, Magri C, et al. The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. Am J Hum Genet. 2004 Nov;75:910-918.
4. Ruiz-Pesini E, Lapena AC, Diez-Sanchez C, et al. Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000;67:682-696.
5. Herrnstadt C, Howell N. An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders. Mitochondrion. 2004;4:791-798.