title: Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier.
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.
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Nuria
authors.initials: N
authors.lastname: Marti Gutierrez
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Morey
authors.affiliation: 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.
authors.forename: Crystal
authors.initials: C
authors.lastname: Van Dyken
authors.affiliation: 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.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Hayama
authors.affiliation: 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.
authors.forename: Yeonmi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tippner-Hedges
authors.affiliation: 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.
authors.forename: Don P
authors.initials: DP
authors.lastname: Wolf
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
authors.affiliation: 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.
authors.forename: Shoukhrat
authors.initials: S
authors.lastname: Mitalipov
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics*; D003433:Crosses, Genetic; D004272:DNA, Mitochondrial / Q000235:genetics; D020964:Embryo Loss / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D012098:Reproduction / Q000235:genetics*; D013045:Species Specificity
chemical_list: D004272:DNA, Mitochondrial