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

Hong Ma, Nuria Marti Gutierrez, Robert Morey, Crystal Van Dyken, Eunju Kang, Tomonari Hayama, Yeonmi Lee, Ying Li, Rebecca Tippner-Hedges, Don P. Wolf, Louise C. Laurent, Shoukhrat Mitalipov

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)283-294
Number of pages12
JournalCell Metabolism
Issue number2
StatePublished - Aug 9 2016

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier'. Together they form a unique fingerprint.

Cite this