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Cell Metab. 2016 Aug 9;24(2):283-94. doi: 10.1016/j.cmet.2016.06.012. Epub 2016 Jul 14.

Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier.

Author information

1
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA; Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
2
Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
3
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA; Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA; Knight Cardiovascular Institute and Departments of Obstetrics and Gynecology, Molecular and Medical Genetics, and Biomedical Engineering, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: mitalipo@ohsu.edu.

Abstract

Vertebrate cells carry two different genomes, nuclear (nDNA) and mitochondrial (mtDNA), both encoding proteins involved in oxidative phosphorylation. Because of the extensive interactions, adaptive coevolution of the two genomes must occur to ensure normal mitochondrial function. To investigate whether incompatibilities between these two genomes could contribute to interspecies reproductive barriers, we performed reciprocal mtDNA replacement (MR) in zygotes between widely divergent Mus m. domesticus (B6) and conplastic Mus m. musculus (PWD) mice. Transfer of MR1 cybrid embryos (B6nDNA-PWDmtDNA) supported normal development of F1 offspring with reduced male fertility but unaffected reproductive fitness in females. Furthermore, donor PWD mtDNA was faithfully transmitted through the germline into F2 and F3 generations. In contrast, reciprocal MR2 (PWDnDNA-B6mtDNA) produced high embryonic loss and stillborn rates, suggesting an association between mitochondrial function and infertility. These results strongly suggest that functional incompatibility between nuclear and mitochondrial genomes contributes to interspecies reproductive isolation in mammals.

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PMID:
27425585
PMCID:
PMC4981548
DOI:
10.1016/j.cmet.2016.06.012
[Indexed for MEDLINE]
Free PMC Article

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