The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development

  1. Marco Colnaghi
  2. Andrew Pomiankowski  Is a corresponding author
  3. Nick Lane
  1. University College London, United Kingdom
  2. UCL Faculty of Life Sciences, United Kingdom

Abstract

Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modelling work has not clarified the issues. Here we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realistic de novo mutation rates and germline development parameters from mouse and humans, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.

Data availability

All code has been posted on Github https://github.com/MarcoColnaghi1990/colnaghi-pomiankowski-lane-elife-2021

Article and author information

Author details

  1. Marco Colnaghi

    Genetics, Evolution and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5641-9324
  2. Andrew Pomiankowski

    Genetics, Evolution and Environment, University College London, London, United Kingdom
    For correspondence
    a.pomiankowski@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5171-8755
  3. Nick Lane

    Genetics, Evolution and Environment, UCL Faculty of Life Sciences, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5433-3973

Funding

Engineering and Physical Sciences Research Council (EP/F500351/1)

  • Andrew Pomiankowski

Engineering and Physical Sciences Research Council (EP/I017909/1)

  • Andrew Pomiankowski

Natural Environment Research Council (NE/R010579/1)

  • Andrew Pomiankowski

Biotechnology and Biological Sciences Research Council (BB/S003681/1)

  • Nick Lane

bgc3 (.none.)

  • Nick Lane

Biotechnology and Biological Sciences Research Council (BB/V003542/1)

  • Marco Colnaghi
  • Andrew Pomiankowski
  • Nick Lane

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany

Publication history

  1. Preprint posted: September 3, 2020 (view preprint)
  2. Received: April 12, 2021
  3. Accepted: July 16, 2021
  4. Accepted Manuscript published: July 19, 2021 (version 1)
  5. Version of Record published: August 4, 2021 (version 2)

Copyright

© 2021, Colnaghi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,337
    Page views
  • 236
    Downloads
  • 6
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Marco Colnaghi
  2. Andrew Pomiankowski
  3. Nick Lane
(2021)
The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development
eLife 10:e69344.
https://doi.org/10.7554/eLife.69344
  1. Further reading

Further reading

    1. Evolutionary Biology
    Paul C Sereno, Nathan Myhrvold ... Lauren L Conroy
    Research Article

    A predominantly fish-eating diet was envisioned for the sail-backed theropod dinosaur Spinosaurus aegyptiacus when its elongate jaws with subconical teeth were unearthed a century ago in Egypt. Recent discovery of the high-spined tail of that skeleton, however, led to a bolder conjecture that S. aegyptiacus was the first fully aquatic dinosaur. The ‘aquatic hypothesis’ posits that S. aegyptiacus was a slow quadruped on land but a capable pursuit predator in coastal waters, powered by an expanded tail. We test these functional claims with skeletal and flesh models of S. aegyptiacus. We assembled a CT-based skeletal reconstruction based on the fossils, to which we added internal air and muscle to create a posable flesh model. That model shows that on land S. aegyptiacus was bipedal and in deep water was an unstable, slow-surface swimmer (<1 m/s) too buoyant to dive. Living reptiles with similar spine-supported sails over trunk and tail are used for display rather than aquatic propulsion, and nearly all extant secondary swimmers have reduced limbs and fleshy tail flukes. New fossils also show that Spinosaurus ranged far inland. Two stages are clarified in the evolution of Spinosaurus, which is best understood as a semiaquatic bipedal ambush piscivore that frequented the margins of coastal and inland waterways.

    1. Computational and Systems Biology
    2. Evolutionary Biology
    Guillem Santamaria, Chen Liao ... Joao B Xavier
    Research Article Updated

    Microbes have disproportionate impacts on the macroscopic world. This is in part due to their ability to grow to large populations that collectively secrete massive amounts of secondary metabolites and alter their environment. Yet, the conditions favoring secondary metabolism despite the potential costs for primary metabolism remain unclear. Here we investigated the biosurfactants that the bacterium Pseudomonas aeruginosa makes and secretes to decrease the surface tension of surrounding liquid. Using a combination of genomics, metabolomics, transcriptomics, and mathematical modeling we show that the ability to make surfactants from glycerol varies inconsistently across the phylogenetic tree; instead, lineages that lost this ability are also worse at reducing the oxidative stress of primary metabolism on glycerol. Experiments with different carbon sources support a link with oxidative stress that explains the inconsistent distribution across the P. aeruginosa phylogeny and suggests a general principle: P. aeruginosa lineages produce surfactants if they can reduce the oxidative stress produced by primary metabolism and have excess resources, beyond their primary needs, to afford secondary metabolism. These results add a new layer to the regulation of a secondary metabolite unessential for primary metabolism but important to change physical properties of the environments surrounding bacterial populations.