Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells

Publication date: Available online 30 June 2016
Source:Cell Reports
Author(s): Auke B.C. Otten, Tom E.J. Theunissen, Josien G. Derhaag, Ellen H. Lambrichs, Iris B.W. Boesten, Marie Winandy, Aafke P.A. van Montfoort, Katsiaryna Tarbashevich, Erez Raz, Mike Gerards, Jo M. Vanoevelen, Bianca J.C. van den Bosch, Marc Muller, Hubert J.M. Smeets
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 × 10⁶ 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.

Graphical abstract

Teaser

Otten et al. describe the mtDNA bottleneck in zebrafish. Oocytes have a high and variable mtDNA copy number, dictating the variation in the mtDNA bottleneck size. Differences in size and timing of the bottleneck between germline and non-germline cells suggest differences in segregation and sensitivity to de novo mtDNA mutations.


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