Cited by 418Evolution and Genetic DynamicsMitochondrial Function and PathologyForensic and Genetic Research

Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice

Jenuth, Jack P., Peterson, Alan C., Shoubridge, Eric A.·1997·Nature Genetics

Abstract

Mammalian mitochondrial DNA (mtDNA) is a highly polymorphic, high-copy-number genome that is maternally inherited. New mutations in mtDNA segregate rapidly in the female germline due to a genetic bottleneck in early oogenesis and as a result most individuals are homoplasmic for a single species of mtDNA. Sequence variants thus accumulate along maternal lineages without genetic recombination. Most of the extant variation in mtDNA in mammalian populations has been assumed to be neutral with respect to selection; however, comparisons of the ratio of replacement to silent nucleotide substitutions between species suggest that the evolution of mammalian mtDNA is not strictly neutral. To test directly whether polymorphic mtDNAs behave as neutral variants, we examined the segregation of two different mtDNA genotypes in the tissues of heteroplasmic mice. We find evidence for random genetic drift in some tissues, but in others strong, tissue-specific and age-related, directional selection for different mtDNA genotypes in the same animal. These surprising data suggest that the coding sequence of mtDNA may represent a compromise between the competing demands of different tissues and point to the existence of unknown, tissue-specific nuclear genes important in the interaction between the nuclear and mitochondrial genomes.

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Crossref · 10.1038/ng0597-93

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  • The first heteroplasmic mice were generated by cytoplasmic fusion of two normal mouse strains carrying distinct haplotypes.

    “The first heteroplasmic mice were generated by cytoplasmic fusion of two normal mouse strains carrying distinct haplotypes [74,169].”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [169]

  • Present evidence suggests that the mutation load detected in the prenatal sample accurately reflects the heteroplasmy levels in other foetal tissues.

    “Whilst there is concern whether the mutation load detected in the prenatal sample would accurately reflect the heteroplasmy levels in other foetal tissues, present evidence suggests that this should not be a problem [169,249].”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [169]

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Authors
Jenuth, J. P., Peterson, A. C., & Shoubridge, E. A.
Affiliations
  • Montreal Neurological Institute and Hospital (CA)
  • McGill University (CA)
Corresponding author
Shoubridge, Eric A.
Venue
Nature Genetics
Published
1997-05
Volume
16
Issue
1
Pages
93-95
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2080844913
Cited by
415
References
21
Citations by year
2026: 2 · 2025: 7 · 2024: 35 · 2023: 12 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 12 · 2018: 11 · 2017: 7 · 2016: 8 · 2015: 22 · 2014: 17 · 2013: 11 · 2012: 12
FWCI
10.51
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
mitochondrial DNA, heteroplasmy, genetic drift, mtDNA polymorphisms, neutral evolution, nuclear-mitochondrial interactions, nuclear genes
MeSH terms
Age Factors, Animals, Animals, Newborn, Blastocyst, Blood Physiological Phenomena, Colon, DNA, Mitochondrial, Female, Kidney, Liver, Male, Mice, Inbred C57BL, Mice, Inbred NZB, Mice, Inbred Strains, Mice, Transgenic, Models, Genetic, Organ Specificity, Selection, Genetic, Spleen, Stem Cells, Genetic Variation, Mice

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