title: Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells.
abstract: We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 × 10(6) mtDNA molecules with high variation between oocytes. During embryogenesis, the mtDNA copy number decreases to ∼170 mtDNA molecules per primordial germ cell (PGC), a number similar to that in mammals, and to ∼50 per non-PGC. These occur at the same developmental stage, implying considerable variation in mtDNA copy number in (non-)PGCs of the same female, dictated by variation in the mature oocyte. The presence of oocytes with low mtDNA numbers, if similar in humans, could explain how (de novo) mutations can reach high mutation loads within a single generation. High mtDNA copy numbers in mature oocytes are established by mtDNA replication during oocyte development. Bottleneck differences between germline and non-germline cells, due to early differentiation of PGCs, may account for different distribution patterns of familial mutations.
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Auke B C
authors.initials: AB
authors.lastname: Otten
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Tom E J
authors.initials: TE
authors.lastname: Theunissen
authors.affiliation: Department of Obstetrics and Gynaecology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Josien G
authors.initials: JG
authors.lastname: Derhaag
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Lambrichs
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Iris B W
authors.initials: IB
authors.lastname: Boesten
authors.affiliation: Laboratory of Organogenesis and Regeneration, GIGA-Research, Univérsité de Liège, 4000 Liège, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Winandy
authors.affiliation: Department of Obstetrics and Gynaecology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Aafke P A
authors.initials: AP
authors.lastname: van Montfoort
authors.affiliation: Institute for Cell Biology, Centre for Molecular Biology of Inflammation, Münster University, 48149 Münster, Germany.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Tarbashevich
authors.affiliation: Institute for Cell Biology, Centre for Molecular Biology of Inflammation, Münster University, 48149 Münster, Germany.
authors.forename: Erez
authors.initials: E
authors.lastname: Raz
authors.affiliation: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University Medical Centre, 6200MD, the Netherlands.
authors.forename: Mike
authors.initials: M
authors.lastname: Gerards
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Jo M
authors.initials: JM
authors.lastname: Vanoevelen
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands.
authors.forename: Bianca J C
authors.initials: BJ
authors.lastname: van den Bosch
authors.affiliation: Laboratory of Organogenesis and Regeneration, GIGA-Research, Univérsité de Liège, 4000 Liège, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Muller
authors.affiliation: Department of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, 6200MD Maastricht, the Netherlands; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University Medical Centre, 6200MD, the Netherlands. Electronic address: bert.smeets@maastrichtuniversity.nl.
authors.forename: Hubert J M
authors.initials: HJ
authors.lastname: Smeets
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial