Comparative genomics reveals insight into the evolutionary origin of massively scrambled genomes

  1. Yi Feng
  2. Rafik Neme
  3. Leslie Y Beh
  4. Xiao Chen
  5. Jasper Braun
  6. Michael W Lu
  7. Laura F Landweber  Is a corresponding author
  1. Columbia University, United States
  2. Universidad del Norte, Colombia
  3. Pacific Biosciences, United States
  4. University of South Florida, United States

Abstract

Ciliates are microbial eukaryotes that undergo extensive programmed genome rearrangement, a natural genome editing process that converts long germline chromosomes into smaller gene-rich somatic chromosomes. Three well-studied ciliates include Oxytricha trifallax, Tetrahymena thermophila and Paramecium tetraurelia, but only the Oxytricha lineage has a massively scrambled genome, whose assembly during development requires hundreds of thousands of precise programmed DNA joining events, representing the most complex genome dynamics of any known organism. Here we study the emergence of such complex genomes by examining the origin and evolution of discontinuous and scrambled genes in the Oxytricha lineage. This study compares six genomes from three species, the germline and somatic genomes for Euplotes woodruffi, Tetmemena sp., and the model ciliate Oxytricha trifallax. To complement existing data, we sequenced, assembled and annotated the germline and somatic genomes of Euplotes woodruffi, which provides an outgroup, and the germline genome of Tetmemena sp.. We find that the germline genome of Tetmemena is as massively scrambled and interrupted as Oxytricha's : 13.6% of its gene loci require programmed translocations and/or inversions, with some genes requiring hundreds of precise gene editing events during development. This study revealed that the earlier-diverged spirotrich, E. woodruffi, also has a scrambled genome, but only roughly half as many loci (7.3%) are scrambled. Furthermore, its scrambled genes are less complex, together supporting the position of Euplotes as a possible evolutionary intermediate in this lineage, in the process of accumulating complex evolutionary genome rearrangements, all of which require extensive repair to assemble functional coding regions. Comparative analysis also reveals that scrambled loci are often associated with local duplications, supporting a gradual model for the origin of complex, scrambled genomes via many small events of DNA duplication and decay.

Data availability

Custom scripts are public on https://github.com/yifeng-evo/Oxytricha_Tetmemena_Euplotes. DNA-seq reads and genome assemblies are available at GenBank under Bioprojects PRJNA694964 (Tetmemena sp.) and PRJNA781979 (Euplotes woodruffi). Genbank accession numbers for genomes are JAJKFJ000000000 (Tetmemena sp. Micronucleus genome), JAJLLS000000000 (Euplotes woodruffi Micronucleus genome), and JAJLLT000000000 (Euplotes woodruffi Macronucleus genome).Three replicates of RNA-seq reads for vegetative cells are available at GenBank under accession numbers of SRR21815378, SRR21815379, SRR21815380 for E. woodruffi and SRR21817702, SRR21817703 and SRR21817704 for Tetmemena sp..MDSs annotations for three species are available at https://doi.org/10.5061/dryad.5dv41ns96 and https://knot.math.usf.edu/mds_ies_db/2022/downloads.html (please select species from the drop-down menu).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Yi Feng

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    No competing interests declared.
  2. Rafik Neme

    Department of Chemistry and Biology, Universidad del Norte, Barranquilla, Colombia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8462-5291
  3. Leslie Y Beh

    Department of Biochemistry, Columbia University, New York, United States
    Competing interests
    Leslie Y Beh, The author is currently employed by Illumina.
  4. Xiao Chen

    Pacific Biosciences, Menlo Park, United States
    Competing interests
    Xiao Chen, employed by Pacific Biosciences.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1432-268X
  5. Jasper Braun

    Department of Mathematics and Statistics, University of South Florida, Tampa, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1250-4399
  6. Michael W Lu

    Department of Biochemistry, Columbia University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4926-8839
  7. Laura F Landweber

    Department of Biochemistry, Columbia University, New York, United States
    For correspondence
    Laura.Landweber@columbia.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7030-8540

Funding

National Institutes of Health (R35GM122555)

  • Yi Feng

National Science Foundation (DMS1764366)

  • Yi Feng

Pew Latin American Fellows Program (no)

  • Rafik Neme

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

Copyright

© 2022, Feng 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

  • 10
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Yi Feng
  2. Rafik Neme
  3. Leslie Y Beh
  4. Xiao Chen
  5. Jasper Braun
  6. Michael W Lu
  7. Laura F Landweber
(2022)
Comparative genomics reveals insight into the evolutionary origin of massively scrambled genomes
eLife 11:e82979.
https://doi.org/10.7554/eLife.82979

Share this article

https://doi.org/10.7554/eLife.82979

Further reading

    1. Evolutionary Biology
    Lucy A Winder, Mirre JP Simons, Terry Burke
    Research Article

    Life-history theory, central to our understanding of diversity in morphology, behaviour, and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness – reproductive effort and survival – questioning the theory’s general validity. We used a meta-analysis to separate the effects of individual quality (positive survival/reproduction correlation) from the costs of reproduction (negative survival/reproduction correlation) using studies of reproductive effort and parental survival in birds. Experimental enlargement of brood size caused reduced parental survival. However, the effect size of brood size manipulation was small and opposite to the effect of phenotypic quality, as we found that individuals that naturally produced larger clutches also survived better. The opposite effects on parental survival in experimental and observational studies of reproductive effort provide the first meta-analytic evidence for theory suggesting that quality differences mask trade-offs. Fitness projections using the overall effect size revealed that reproduction presented negligible costs, except when reproductive effort was forced beyond the maximum level observed within species, to that seen between species. We conclude that there is little support for the most fundamental life-history trade-off, between reproductive effort and survival, operating within a population. We suggest that within species the fitness landscape of the reproduction–survival trade-off is flat until it reaches the boundaries of the between-species fast–slow life-history continuum. Our results provide a quantitative explanation as to why the costs of reproduction are not apparent and why variation in reproductive effort persists within species.

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology
    Gülnihal Kavaklioglu, Alexandra Podhornik ... Christian Seiser
    Research Article

    Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.