Lost in the zygote: the dilution of paternal mtDNA upon fertilization

Abstract

The mechanisms by which paternal inheritance of mitochondrial DNA (mtDNA) (paternal leakage) and, subsequently, recombination of mtDNA are prevented vary in a speciesspecific manner with one mechanism in common: paternally derived mtDNA is assumed to be vastly outnumbered by maternal mtDNA in the zygote. To date, this dilution effect has only been described for two mammalian species, human and mouse. Here, we estimate the mtDNA content of chinook salmon oocytes to evaluate the dilution effect operating in another vertebrate; the first such study outside a mammalian system. Employing real-time PCR, we determined the mtDNA content of chinook salmon oocytes to be 3.2 Â 10 9 ± 1.0 Â 10 9 , and recently, we determined the mtDNA content of chinook salmon sperm to be 5.73 ± 2.28 per gamete. Accordingly, the ratio of paternal-to-maternal mtDNA if paternal leakage occurs is estimated to be 1:5.5 Â 10 8 . This contribution of paternal mtDNA to the overall mtDNA pool in salmon zygotes is three to five orders of magnitude smaller than those revealed for the mammalian system, strongly suggesting that paternal inheritance of mtDNA per offspring will be much less likely in this system than in mammals.

The Strength and Timing of the Mitochondrial Bottleneck in Salmon Suggests a Conserved Mechanism in Vertebrates

“…The mean (and 95% CIs) are 1.92% (1.59%–2.32%) for mothers, 1.67% (1.38%–2.03%) for eggs, and 1.18% (0.95%–1.49%) for offspring. Our lower N e estimate of 80.3 is approximately 4.0×10 7 -fold less than mtDNA copy number in mature salmon oocytes, estimated to harbor some 3.2×10 9 mtDNA molecules [39].…”

“…Both sites confer synonymous changes and are located in the mitochondrial gene mt-nd1 , at nucleotide positions 4149 and 4316 (NCBI:NC_002980) [39]. An A/G polymorphism (A = wildtype) was found at position 4149 (A4149G), and a C/T polymorphism (T = wildtype) at position 4316 (T4316C).…”

Persistence and Transcription of Paternal mtDNA Dependent on the Delivery Strategy Rather than Mitochondria Source in Fish Embryos

“…In medaka fish, the sperm mtDNAs was rapidly digested just after fertilization, and digestion of paternal mtDNA was achieved before total destruction of mitochondrial structures [24]. The results obtained in this study suggest the presence of an embryonic factor or factors responsible for elimination and/or transcriptional quiescence of fertilization-delivered sperm mtDNA but not MT injection-delivered paternal mtDNA prior to birth.…”

“…Distinct molecular mechanisms to prevent inheritance of paternal mtDNA have been described in various species. The pre-fertilization mechanism is proposed in Chinook salmon_ENREF_26, where sperms have fewer mtDNA copies for delivery at fertilization of the eggs [24]. In Drosophila, mtDNA is degraded during spermatogenesis, and mature sperms lack any mtDNA and do not deliver paternal mtDNA to ensure MUI [5].…”

“…The mechanism of selective elimination of parental mitochondrial DNA in fish is only sporadically reported [8,19,24]. In medaka fish, the sperm mtDNAs was rapidly digested just after fertilization, and digestion of paternal mtDNA was achieved before total destruction of mitochondrial structures [24].…”