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

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Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice

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

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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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Additional file 10 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755207
Additional file 36 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755285
Additional file 22 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755243
Additional file 35 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755282
Additional file 9 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755204
Additional file 13 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755216
Additional file 2 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755183
Additional file 16 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755225
Additional file 39 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755294
Additional file 24 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755249
Additional file 8 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755201
Additional file 32 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755273
Additional file 31 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755270
Additional file 15 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755222
Additional file 7 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755198
Additional file 20 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755237
Additional file 30 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755267
Additional file 11 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755210
Additional file 17 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755228
Additional file 21 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755240
Additional file 34 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755279
Additional file 38 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755291
Additional file 1 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755180
Additional file 14 of Single-mitochondrion sequencing uncovers distinct mutational patterns and heteroplasmy landscape in mouse astrocytes and neurons
Kadam, P. S., Yang, Z., Lu, Y., Zhu, H., Atiyas, Y., Shah, N., Fisher, S., Nordgren, E., Kim, J., Issadore, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26755219

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.
ORCID: Peterson, Alan C.
Shoubridge, Eric A.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1997-05
Volume: 16
Issue: 1
Pages: 93-95
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0597-93
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
Licence: www.springer.com/tdm (tdm)
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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Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice

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