Wolff JN, White DJ, Woodhams M, White HE, Gemmell NJ. The strength and timing of the mitochondrial bottleneck in salmon suggests a conserved mechanism in vertebrates. PLoS ONE 6: e20522

School of Biological Sciences, University of Canterbury, Christchurch, Canterbury, New Zealand.
PLoS ONE (Impact Factor: 3.23). 05/2011; 6(5):e20522. DOI: 10.1371/journal.pone.0020522
Source: PubMed


In most species mitochondrial DNA (mtDNA) is inherited maternally in an apparently clonal fashion, although how this is achieved remains uncertain. Population genetic studies show not only that individuals can harbor more than one type of mtDNA (heteroplasmy) but that heteroplasmy is common and widespread across a diversity of taxa. Females harboring a mixture of mtDNAs may transmit varying proportions of each mtDNA type (haplotype) to their offspring. However, mtDNA variants are also observed to segregate rapidly between generations despite the high mtDNA copy number in the oocyte, which suggests a genetic bottleneck acts during mtDNA transmission. Understanding the size and timing of this bottleneck is important for interpreting population genetic relationships and for predicting the inheritance of mtDNA based disease, but despite its importance the underlying mechanisms remain unclear. Empirical studies, restricted to mice, have shown that the mtDNA bottleneck could act either at embryogenesis, oogenesis or both. To investigate whether the size and timing of the mitochondrial bottleneck is conserved between distant vertebrates, we measured the genetic variance in mtDNA heteroplasmy at three developmental stages (female, ova and fry) in chinook salmon and applied a new mathematical model to estimate the number of segregating units (N(e)) of the mitochondrial bottleneck between each stage. Using these data we estimate values for mtDNA Ne of 88.3 for oogenesis, and 80.3 for embryogenesis. Our results confirm the presence of a mitochondrial bottleneck in fish, and show that segregation of mtDNA variation is effectively complete by the end of oogenesis. Considering the extensive differences in reproductive physiology between fish and mammals, our results suggest the mechanism underlying the mtDNA bottleneck is conserved in these distant vertebrates both in terms of it magnitude and timing. This finding may lead to improvements in our understanding of mitochondrial disorders and population interpretations using mtDNA data.

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    • "The concept of a genetic bottleneck for the transmission of mtDNA was initially based on the observation that, despite a high copy number in the oocyte, sequence variants segregate rapidly between generations (Hauswirth & Laipis 1982; Olivo et al. 1983). Subsequently , the size and timing of the bottleneck has been studied in a variety of animals (Wai, Teoli & Shoubridge 2008; Wolff et al. 2011). Moreover, mitophagy, the mitochondrial degradation by autophagy, has been shown to be selective and may also act as an evolutionary process that selectively removes dysfunctional mitochondria (Kim, Rodriguez-Enriquez & Lemasters 2007). "
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    ABSTRACT: 1. The vast majority of studies employing mtDNA in evolutionary biology and ecology have used it as a means to infer demographic and historical patterns without pondering the underly-ing functional implications. In contrast, the biochemical and medical communities often aim to understand the influence of specific mtDNA mutations on mitochondrial functions, but rarely consider the evolutionary and ecological implications. 2. Ongoing research has shown that mtDNA mutations can profoundly affect mitochondrial function in humans and other animals. If the mutation (or set of mutations) is pathogenic, mitochondrial malfunction may be detected from early age. In nature, however, most muta-tions are not highly deleterious and may exist at intermediate frequency in populations. 3. In this review, we suggest that knowledge of the underlying biochemistry and functions of mitochondria can facilitate a more complete determination of the evolutionary dynamics of mtDNA and its influence on the life-history traits of organisms. With this approach, it is possi-ble to use biochemistry to link the genotype with the phenotype. 4. After reviewing the literature, we conclude that there can be physiological and evolutionary trade-offs in the way that mitochondrial mutations can affect age classes and/or fitness compo-nents and that these effects may depend on the environment. Through these trade-offs, it may be possible for specific mtDNA mutations to have unequal fitness in different nuclear genetic backgrounds and also in different environments.
    Functional Ecology 12/2013; 28(1). DOI:10.1111/1365-2435.12177 · 4.83 Impact Factor
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    • "carrying intensive length variations in this case) repopulate the offspring of next generation from the germ line [21], [22], [25], [26], [27], [75]. No reduction of mtDNA content in early primordial germ cells [76], [77] but the relaxed amplification of a subpopulation of mtDNA genomes in early oogenesis [23] or during postnatal folliculogenesis [78] in mice or by the end of oogenesis in fish [32] is suggested to have contributed to the random mtDNA segregation [31]. However, the differences in the properties of heteroplasmic mtDNA structures (point mutation v.s. "
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    ABSTRACT: The animal mitochondrial DNA (mtDNA) length polymorphism and heteroplasmy are accepted to be universal. Here we report the lack of structural variation but the presence of length polymorphism as well as heteroplasmy in mtDNA control region of an endangered avian species - the Crested Ibis (Nipponia nippon). The complete control region was directly sequenced while the distribution pattern and inheritance of the length variations were examined using both direct sequencing and genotyping of the PCR fragments from captive birds with pedigrees, wild birds and a historical specimen. Our results demonstrated that there was no structural variation in the control region, however, different numbers of short tandem repeats with an identical motif of CA3CA2CA3 at the 3'-end of the control region determined the length polymorphisms among and heteroplasmy within individual birds. There were one to three predominant fragments in every bird; nevertheless multiple minor fragments coexist in all birds. These extremely high polymorphisms were suggested to have derived from the 'replication slippage' of a perfect microsatellite evolution following the step-wise mutational model. The patterns of heteroplasmy were found to be shifted between generations and among siblings but rather stable between blood and feather samples. This study provides the first evidence of a very extensive mtDNA length polymorphism and heteroplasmy in the highly inbred Crested Ibis which carries an mtDNA genome lack of structural genetic diversity. The analysis of pedigreed samples also sheds light on the transmission of mtDNA length heteroplasmy in birds following the genetic bottleneck theory. Further research focusing on the generation and transmission of particular mtDNA heteroplasmy patterns in single germ line of Crested Ibis is encouraged by this study.
    PLoS ONE 06/2013; 8(6):e66324. DOI:10.1371/journal.pone.0066324 · 3.23 Impact Factor
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    • "We can only speculate why mechanisms to prevent paternal leakage fail in single pairs. If it was a purely stochastic phenomenon, then we would expect the distribution of affected individuals carrying paternal mtDNA to be even among all offspring and not pair specific (Bergstrom and Pritchard, 1998; Wolff et al., 2011). Pair specificity instead requires one or more mechanisms promoting maternal inheritance to fail in single pairs, allowing for the repeated occurrence among a pair's offspring. "
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    ABSTRACT: Maternal inheritance is one of the hallmarks of animal mitochondrial DNA (mtDNA) and central to its success as a molecular marker. This mode of inheritance and subsequent lack of heterologous recombination allows us to retrace evolutionary relationships unambiguously down the matriline and without the confounding effects of recombinant genetic information. Accumulating evidence of biparental inheritance of mtDNA (paternal leakage), however, challenges our current understanding of how this molecule is inherited. Here, using Drosophila simulans collected from an East African metapopulation exhibiting recurring mitochondrial heteroplasmy, we conducted single fly matings and screened F1 offspring for the presence of paternal mtDNA using allele-specific PCR assays (AS-PCR). In all, 27 out of 4092 offspring were identified as harboring paternal mtDNA, suggesting a frequency of 0.66% paternal leakage in this species. Our findings strongly suggest that recurring mtDNA heteroplasmy as observed in natural populations of Drosophila simulans is most likely caused by repeated paternal leakage. Our findings further suggest that this phenomenon to potentially be an integral part of mtDNA inheritance in these populations and consequently of significance for mtDNA as a molecular marker.Heredity advance online publication, 26 September 2012; doi:10.1038/hdy.2012.60.
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