Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load

  1. Beatriz Navarro-Dominguez
  2. Ching-Ho Chang
  3. Cara L Brand
  4. Christina A Muirhead
  5. Daven C Presgraves  Is a corresponding author
  6. Amanda M Larracuente  Is a corresponding author
  1. University of Granada, Spain
  2. University of Rochester, United States

Abstract

Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation resulting in preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing one of a pair of alternative alleles. While at least two loci are important for male drive- the driver and the target- linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world, and have implications for supergene evolution broadly.

Data availability

Raw sequence data are deposited in NCBI's short read archive under project accession PRJNA649752. All code for data analysis and figure generation is available in Github (https://github.com/bnavarrodominguez/sd_popgen). Data and code will be deposited in Dryad digital repository.

The following data sets were generated

Article and author information

Author details

  1. Beatriz Navarro-Dominguez

    Department of Genetics, University of Granada, Granada, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4077-8696
  2. Ching-Ho Chang

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9361-1190
  3. Cara L Brand

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christina A Muirhead

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Daven C Presgraves

    Department of Biology, University of Rochester, Rochester, United States
    For correspondence
    daven.presgraves@rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Amanda M Larracuente

    Department of Biology, University of Rochester, Rochester, United States
    For correspondence
    alarracu@UR.Rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5944-5686

Funding

National Institute of General Medical Sciences (R35 GM119515)

  • Amanda M Larracuente

Stephen Biggar and Elisabeth Asaro Fellowship in Data Science (NA)

  • Amanda M Larracuente

David and Lucile Packard Foundation

  • Daven C Presgraves

University of Rochester funds

  • Daven C Presgraves

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

Reviewing Editor

  1. Detlef Weigel, Max Planck Institute for Biology Tübingen, Germany

Version history

  1. Preprint posted: December 24, 2021 (view preprint)
  2. Received: April 3, 2022
  3. Accepted: April 20, 2022
  4. Accepted Manuscript published: April 29, 2022 (version 1)
  5. Accepted Manuscript updated: May 3, 2022 (version 2)
  6. Version of Record published: May 20, 2022 (version 3)

Copyright

© 2022, Navarro-Dominguez 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

  • 1,898
    Page views
  • 401
    Downloads
  • 7
    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. Beatriz Navarro-Dominguez
  2. Ching-Ho Chang
  3. Cara L Brand
  4. Christina A Muirhead
  5. Daven C Presgraves
  6. Amanda M Larracuente
(2022)
Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load
eLife 11:e78981.
https://doi.org/10.7554/eLife.78981

Share this article

https://doi.org/10.7554/eLife.78981

Further reading

    1. Cell Biology
    2. Evolutionary Biology
    Jonathan E Phillips, Duojia Pan
    Research Advance

    The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.

    1. Evolutionary Biology
    2. Immunology and Inflammation
    Zachary Paul Billman, Stephen Bela Kovacs ... Edward A Miao
    Research Article

    Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA–D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.