Mitochondrial DNA in Human Diversity and Health: From the Golden Age to the Omics Era

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Aug 26

PMID 37628587

Authors

Candela L Hernandez

Affiliations

Soon will be listed here.

Abstract

Mitochondrial DNA (mtDNA) is a small fraction of our hereditary material. However, this molecule has had an overwhelming presence in scientific research for decades until the arrival of high-throughput studies. Several appealing properties justify the application of mtDNA to understand how human populations are-from a genetic perspective-and how individuals exhibit phenotypes of biomedical importance. Here, I review the basics of mitochondrial studies with a focus on the dawn of the field, analysis methods and the connection between two sides of mitochondrial genetics: anthropological and biomedical. The particularities of mtDNA, with respect to inheritance pattern, evolutionary rate and dependence on the nuclear genome, explain the challenges of associating mtDNA composition and diseases. Finally, I consider the relevance of this single locus in the context of omics research. The present work may serve as a tribute to a tool that has provided important insights into the past and present of humankind.

Citing Articles

The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.

Van Der Kelen A, Li Piani L, Mertens J, Regin M, Couvreu de Deckersberg E, Van de Velde H Hum Reprod Open. 2025; 2025(1):hoae074.

PMID: 39830711 PMC: 11739621. DOI: 10.1093/hropen/hoae074.

References

Hervella M, Svensson E, Alberdi A, Gunther T, Izagirre N, Munters A . The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa. Sci Rep. 2016; 6:25501. PMC: 4872530. DOI: 10.1038/srep25501. View

Clima R, Preste R, Calabrese C, Diroma M, Santorsola M, Scioscia G . HmtDB 2016: data update, a better performing query system and human mitochondrial DNA haplogroup predictor. Nucleic Acids Res. 2016; 45(D1):D698-D706. PMC: 5210550. DOI: 10.1093/nar/gkw1066. View

Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace D . Effects of purifying and adaptive selection on regional variation in human mtDNA. Science. 2004; 303(5655):223-6. DOI: 10.1126/science.1088434. View

Crispim D, Canani L, Gross J, Tschiedel B, Souto K, Roisenberg I . The European-specific mitochondrial cluster J/T could confer an increased risk of insulin-resistance and type 2 diabetes: an analysis of the m.4216T > C and m.4917A > G variants. Ann Hum Genet. 2006; 70(Pt 4):488-95. DOI: 10.1111/j.1469-1809.2005.00249.x. View

Fregel R, Cabrera V, Larruga J, Abu-Amero K, Gonzalez A . Carriers of Mitochondrial DNA Macrohaplogroup N Lineages Reached Australia around 50,000 Years Ago following a Northern Asian Route. PLoS One. 2015; 10(6):e0129839. PMC: 4460043. DOI: 10.1371/journal.pone.0129839. View

Maitra A, Cohen Y, Gillespie S, Mambo E, Fukushima N, Hoque M . The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Genome Res. 2004; 14(5):812-9. PMC: 479107. DOI: 10.1101/gr.2228504. View

Oversti S, Palo J . Variation in the Substitution Rates among the Human Mitochondrial Haplogroup U Sublineages. Genome Biol Evol. 2022; 14(7). PMC: 9250076. DOI: 10.1093/gbe/evac097. View

Posth C, Wissing C, Kitagawa K, Pagani L, van Holstein L, Racimo F . Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals. Nat Commun. 2017; 8:16046. PMC: 5500885. DOI: 10.1038/ncomms16046. View

van der Walt J, Nicodemus K, Martin E, Scott W, Nance M, Watts R . Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet. 2003; 72(4):804-11. PMC: 1180345. DOI: 10.1086/373937. View

10.

Sosa M, Ashok Sivakumar I, Maragh S, Veeramachaneni V, Hariharan R, Parulekar M . Next-generation sequencing of human mitochondrial reference genomes uncovers high heteroplasmy frequency. PLoS Comput Biol. 2012; 8(10):e1002737. PMC: 3486893. DOI: 10.1371/journal.pcbi.1002737. View

11.

Govindaraj P, Khan N, Rani B, Rani D, Selvaraj P, Jyothi V . Mitochondrial DNA variations associated with hypertrophic cardiomyopathy. Mitochondrion. 2013; 16:65-72. DOI: 10.1016/j.mito.2013.10.006. View

12.

Gaweda-Walerych K, Maruszak A, Safranow K, Bialecka M, Klodowska-Duda G, Czyzewski K . Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort. J Neural Transm (Vienna). 2008; 115(11):1521-6. DOI: 10.1007/s00702-008-0121-9. View

13.

Singh L, Ennis B, Loneragan B, Tsao N, Lopez Sanchez M, Li J . MitoScape: A big-data, machine-learning platform for obtaining mitochondrial DNA from next-generation sequencing data. PLoS Comput Biol. 2021; 17(11):e1009594. PMC: 8610268. DOI: 10.1371/journal.pcbi.1009594. View

14.

Soto-Hermida A, Fernandez-Moreno M, Oreiro N, Fernandez-Lopez C, Pertega S, Cortes-Pereira E . Mitochondrial DNA (mtDNA) haplogroups influence the progression of knee osteoarthritis. Data from the Osteoarthritis Initiative (OAI). PLoS One. 2014; 9(11):e112735. PMC: 4229258. DOI: 10.1371/journal.pone.0112735. View

15.

Senovska A, Drozdova E, Vaculik O, Pardy F, Brzobohata K, Fialova D . Cost-effective straightforward method for captured whole mitogenome sequencing of ancient DNA. Forensic Sci Int. 2020; 319:110638. DOI: 10.1016/j.forsciint.2020.110638. View

16.

Achilli A, Perego U, Lancioni H, Olivieri A, Gandini F, Hooshiar Kashani B . Reconciling migration models to the Americas with the variation of North American native mitogenomes. Proc Natl Acad Sci U S A. 2013; 110(35):14308-13. PMC: 3761611. DOI: 10.1073/pnas.1306290110. View

17.

Parson W, Dur A . EMPOP--a forensic mtDNA database. Forensic Sci Int Genet. 2008; 1(2):88-92. DOI: 10.1016/j.fsigen.2007.01.018. View

18.

Behar D, Harmant C, Manry J, van Oven M, Haak W, Martinez-Cruz B . The Basque paradigm: genetic evidence of a maternal continuity in the Franco-Cantabrian region since pre-Neolithic times. Am J Hum Genet. 2012; 90(3):486-93. PMC: 3309182. DOI: 10.1016/j.ajhg.2012.01.002. View

19.

Hernandez C, Pita G, Cavadas B, Lopez S, Sanchez-Martinez L, Dugoujon J . Human Genomic Diversity Where the Mediterranean Joins the Atlantic. Mol Biol Evol. 2019; 37(4):1041-1055. PMC: 7086172. DOI: 10.1093/molbev/msz288. View

20.

Taylor R, Taylor G, Durham S, Turnbull D . The determination of complete human mitochondrial DNA sequences in single cells: implications for the study of somatic mitochondrial DNA point mutations. Nucleic Acids Res. 2001; 29(15):E74-4. PMC: 55839. DOI: 10.1093/nar/29.15.e74. View