Skip to main content

Advertisement

Log in

Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

We report new results from the re-analysis of 672 complete mitochondrial (mtDNA) genomes of unrelated Japanese individuals stratified into seven equal sized groups by the phenotypes: diabetic patients, diabetic patients with severe angiopathy, healthy non-obese young males, obese young males, patients with Alzheimer’s disease, patients with Parkinson’s disease and centenarians. Each phenotype had 96 samples over 27 known haplogroups: A, B4a, B4b, B4c, B*, B5, D*, F1, F2, M*, M7a, M7b, M8, M9, D4a, D4b1, D4b2, D4d, D4e, D4g, D4h, D5, G, Z, M*, N9a, and N9b. A t-test comparing the fraction of samples in a haplogroup to healthy young males showed a significant enrichment of haplogroups D4a, D5, and D4b2 in centenarians. The D4b2 enrichment was limited to a subgroup of 40 of 61 samples which had the synonymous mutation 9296C > T. We identified this cluster as a distinct haplogroup and labeled it as D4b2b. Using an exhaustive procedure, we constructed the complete list of “mutation patterns” for centenarians and showed that the most significant patterns were in D4a, D5, and D4b2b. We argue that if a selection for longevity appeared only once, it was probably an autosomal event which could be dated to after the appearance of the D mega-group but before the coalescent time of D4a, D5, and D4b2b. Using a simple procedure, we estimated that this event occurred 24.4 ± 0.9 kYBP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abrams PA (2004) Evolutionary biology: mortality and lifespan. Nature 431:1048

    Article  PubMed  CAS  Google Scholar 

  • Alexe G, Alexe S, Crama Y, Foldes S, Hammer PL, Simeone B (2004) Consensus algorithms for the generation of all maximal bicliques. Discrete Appl Math 145:11–21

    Article  Google Scholar 

  • Alexe G, Hammer PL (2006) Spanned patterns for the logical analysis of data. Discrete Appl Math 154:1039–1049

    Article  Google Scholar 

  • Bazin E, Glemin S, Galtier N (2006) Population size does not influence mitochondrial genetic diversity in animals. Science 312:570–572

    Article  PubMed  CAS  Google Scholar 

  • Brandon MC, Lott MT, Nguyen KC, Spolim S, Navathe SB, Baldi P, Wallace DC (2005) MITOMAP: a human mitochondrial genome database—2004 update. Nucleic Acids Res 33:D611–D613

    Article  PubMed  CAS  Google Scholar 

  • de Grey ADNJ (2002) The mitochondrial free radical theory of aging. Landes Bioscience, Austin

    Google Scholar 

  • Elson JL, Herrnstadt C, Preston G, Thal L, Morris CM, Edwardson JA, Beal MF, Turnbull DM, Howell N (2006) Does the mitochondrial genome play a role in the etiology of Alzheimer’s disease? Hum genet 119:241–254

    Article  PubMed  CAS  Google Scholar 

  • Hawkes K (2004) Human longevity: the grandmother effect. Nature 428:128–129

    Article  PubMed  CAS  Google Scholar 

  • Hawkes K, O’Connell JF, Jones NG, Alvarez H, Charnov EL (1998) Grandmothering, menopause, and the evolution of human life histories. Proc Natl Acad Sci USA 95:1336–1339

    Article  PubMed  CAS  Google Scholar 

  • Ingman M, Gyllensten U (2006) mtDB: human mitochondrial genome database, a resource for population genetics and medical sciences. Nucleic Acids Res 34:D749–D751

    Article  PubMed  CAS  Google Scholar 

  • Ingman M, Kaessmann H, Paabo S, Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408:708–713

    Article  PubMed  CAS  Google Scholar 

  • Jolliffe IT (1986) Principal component analysis. Springer, New York

  • Kazuno AA, Munakata K, Nagai T, Shimozono S, Tanaka M, Yoneda M, Kato N, Miyawaki A, Kato T (2006) Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics. PLoS Genet 2:e128

    Article  PubMed  Google Scholar 

  • Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, Zhu CL, Wu SF, Torroni A, Zhang YP (2006) Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations. Hum Mol Genet 15:2076–2086

    Article  PubMed  CAS  Google Scholar 

  • Lewis K (1999) Human longevity: an evolutionary approach. Mech Ageing Dev 109:43–51

    Article  PubMed  CAS  Google Scholar 

  • Monti S, Tamayo P, Mesirov J, Golub1 T (2003) Consensus clustering: a resampling-based method for class discovery and visualization of gene expression microarray data machine learning 52:91–118

  • Myers E, Miller W (1988) Optimal alignments in linear space. CABIOS 4:11–17

    PubMed  CAS  Google Scholar 

  • Niemi AK, Moilanen JS, Tanaka M, Hervonen A, Hurme M, Lehtimaki T, Arai Y, Hirose N, Majamaa K (2005) A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects. Eur J Hum Genet 13:166–170

    Article  PubMed  CAS  Google Scholar 

  • Rousseeuw PJ (1987) Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J Comput Appl Math 20:53–65

    Article  Google Scholar 

  • Strehl A, Ghosh J, Cardie C (2003) Cluster ensembles: a knowledge reuse framework for combining multiple partitions. J Mach Learn Res 3:583–617

    Article  Google Scholar 

  • Tanaka M, Cabrera VM, Gonzalez AM, Larruga JM, Takeyasu T, Fuku N, Guo LJ, et al (2004) Mitochondrial genome variation in eastern Asia and the peopling of Japan. Genome Res 14:1832–1850

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K (1998) Mitochondrial genotype associated with longevity. Lancet 351:185–186

    Article  PubMed  CAS  Google Scholar 

  • Yen MY, Wang AG, Wei YH (2006) Leber’s hereditary optic neuropathy: a multifactorial disease. Prog Retin Eye Res 25:381–396

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Support Project for Database Development from the Japan Science and Technology Corporation (to M. T.), Grants-in-Aid for Scientific Research (C2-10832009, A2-15200051) and for Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (to M. T.), and by grants BMC2001-3511 and COF2002-015 (to V. M. C.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Gyan Bhanot or Masashi Tanaka.

Additional information

Gabriela Alexe and Noriyuki Fuku are joint first authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

439_2007_330_MOESM1_ESM.xls

Supplementary_Table_1. Binary matrix of mutations for all samples and their phenotypes showing all polymorphic loci with respect to rCRS. A non-mutated locus is represented by 0, a mutated locus by 1. Haplogroup assignments are also shown. We list both haplogroups assigned to the sample in the literature and the haplogroup from consensus ensemble clustering and bootstrap analysis. Binary table showing mutations with respect to rCRS for all samples, including phenotype labels. The phenotype labels are from Ref 10 and correspond to the following: JD: Diabetics with Angiopathy, ND: Diabetics without Angiopathy, HN: Healthy Normals, ON: Obese Normals, KA: Alzheimer's Disease Patients, PD: Parkinson's disease patients, TC/GC: Centenarians. (xls 1243 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alexe, G., Fuku, N., Bilal, E. et al. Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a, and D5 in the Japanese population. Hum Genet 121, 347–356 (2007). https://doi.org/10.1007/s00439-007-0330-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-007-0330-6

Keywords

Navigation