Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck.

David M. Edwards,Iain G. Johnston,Joanna M. Chustecki,Arunas L. Radzvilavicius,Konstantinos Giannakis,Robert C. Glastad,Ellen C. Røyrvik,Thomas B.L. Kirkwood

doi:10.1371/journal.pbio.3001153

David M. Edwards, Iain G. Johnston + Show 6 more

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https://doi.org/10.1371/journal.pbio.3001153

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Abstract

Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic "bottleneck" increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller's ratchet-the gradual buildup of deleterious oDNA mutations? Here, we construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. We apply this comprehensive theory to characterise the animal bottleneck with recent single-cell observations in diverse mouse models. Further, we show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). Genomic, transcriptomic, and structural datasets across eukaryotes support this mechanism for generating beneficial variance without a germline bottleneck. This framework explains puzzling oDNA differences across taxa, suggesting how Muller's ratchet is avoided in different eukaryotes.

Highlights

IntroductionMitochondrial DNA (mtDNA) and plastid DNA (ptDNA) play vital roles in eukaryotic cells [1,2]
In S2 Fig, we further demonstrate the use of Eq 1 to compare different hypothesised mechanisms (including subsampling and reamplification (iv)+(v) and partitioning of Mitochondrial DNA (mtDNA) clusters nc>1) to data on the mouse germline bottleneck using the NZB-BALB/c model [16]
We have quantitatively shown how different cellular and subcellular mechanisms can contribute to the increase of heteroplasmy level variance, and propose that different eukaryotic taxa use different combinations of these mechanisms (Fig 4). This beneficial cell-to-cell variability provides a substrate upon which purifying selection can act, circumventing Muller’s ratchet and preventing mutational meltdown of organelle populations. This theory can be applied across eukaryotes—both providing new quantitative insights on the animal germline bottleneck and describing mechanisms supporting organelle DNA (oDNA) segregation in nonanimal eukaryotes

Summary

Introduction

Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) play vital roles in eukaryotic cells [1,2]. MtDNA encodes bioenergetic machinery in eukaryotes, including the most central aspects of the electron transport chain [3]. PtDNA encodes many of the core proteins of the complexes involved in photosynthetic electron transfer in eukaryotic photoautotrophs. Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) play vital roles in eukaryotic cells [1,2]. mtDNA encodes bioenergetic machinery in eukaryotes, including the most central aspects of the electron transport chain [3]. ptDNA encodes many of the core proteins of the complexes involved in photosynthetic electron transfer in eukaryotic photoautotrophs.

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