Somatic Programmed DNA Elimination is widespread in free-living Rhabditidae nematodes
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eLife Assessment
In this manuscript, the authors investigate programmed DNA elimination (PDE) across nematodes using a large-scale cytological approach. This work is potentially significant because it expands PDE beyond a few known nematodes to a much broader set of Rhabditidae species, providing an important resource for investigating PDE's evolutionary origins and functions. The strength of evidence, however, is incomplete; the technique used to evaluate PDE is insufficient to provide unambiguous support for the phenomenon, so additional methods, such as genomic sequencing from a few species spanning the range of elimination levels, would be required to confirm these findings. This research would be of interest to geneticists, evolutionary biologists, and those working on the regulation of genome integrity.
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Abstract
All cells of a multicellular organism usually share an identical genome, faithfully transmitted through successive divisions. Yet, a number of animal species deviate from this dogma, as parts of their DNA are systematically eliminated in all their somatic nuclei, in a process called Programmed DNA Elimination (PDE). PDE leads to the unexpected reorganisation of the genome at every generation in all somatic cells but its molecular mechanism, evolutionary origins, and functional significance remain unknown. This lack of understanding partially stems from limitations in genetically tractable model species.
PDE can target an entire chromosome, or involve chromosome fragmentation followed by selective fragment retention and elimination, raising further questions on genome stability, genome integrity and mechanisms of DNA repair. PDE by chromosome fragmentation has been described in parasitic nematodes in the family Ascarididae, copepods in the genus Cyclops and unicellular ciliates. More recently, PDE has been discovered in three non-parasitic, lab-tractable nematode species from the Rhabditidae family, opening new perspectives.
In this study, we used cytological approaches to screen 25 new Rhabditidae species for PDE. We found evidence of PDE in 17 species. Our work reveals that PDE is present in 12 out of 17 tested genera, demonstrating its widespread presence in Rhabditidae nematodes, with the notable exception of C. elegans. Genetic tools have already been established for some species. This work provides a collection of lab-tractable species that can be used to test many aspects of somatic Programmed DNA Elimination by chromosome fragmentation in animals.
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eLife Assessment
In this manuscript, the authors investigate programmed DNA elimination (PDE) across nematodes using a large-scale cytological approach. This work is potentially significant because it expands PDE beyond a few known nematodes to a much broader set of Rhabditidae species, providing an important resource for investigating PDE's evolutionary origins and functions. The strength of evidence, however, is incomplete; the technique used to evaluate PDE is insufficient to provide unambiguous support for the phenomenon, so additional methods, such as genomic sequencing from a few species spanning the range of elimination levels, would be required to confirm these findings. This research would be of interest to geneticists, evolutionary biologists, and those working on the regulation of genome integrity.
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Reviewer #1 (Public review):
Summary:
Launay et al., conducted a screen of PDE in 25 new Rhabditidae species through cytological approaches and found PDE is detected in 17 out of 25 species, representing 12 out of 17 genera within the family. This work is significant because it expands PDE from a few known nematodes to a much broader set of Rhabditidae species.
Strengths:
By demonstrating PDE across many genera with the exception of C. elegans and some other Caenorhabditis species, the study provides an important resource for investigating PDE's evolutionary origins, mechanisms of genome reorganization and DNA repair, and its functional consequences.
Most of the observed PDEs were supported by solid evidence through a survey-style cytological screen (PDE detected in 17/25 species and in 12/17 genera), which supports the main claim of …
Reviewer #1 (Public review):
Summary:
Launay et al., conducted a screen of PDE in 25 new Rhabditidae species through cytological approaches and found PDE is detected in 17 out of 25 species, representing 12 out of 17 genera within the family. This work is significant because it expands PDE from a few known nematodes to a much broader set of Rhabditidae species.
Strengths:
By demonstrating PDE across many genera with the exception of C. elegans and some other Caenorhabditis species, the study provides an important resource for investigating PDE's evolutionary origins, mechanisms of genome reorganization and DNA repair, and its functional consequences.
Most of the observed PDEs were supported by solid evidence through a survey-style cytological screen (PDE detected in 17/25 species and in 12/17 genera), which supports the main claim of widespread occurrence.
Weaknesses:
Although most PDE claims are supported by solid evidence, some of the existing data do not describe the depth of characterization, e.g., how many replicates were conducted for each species? How reproducible are the claimed PDEs between embryos in terms of timing and cell identities destined for PDE? Is it possible to validate a subset of PDE with independent evidence, especially for those with marginal PDE? This is important because some dying embryos may fail to maintain their chromosome integrity and release some of the broken DNAs, some others may suffer from noise such as intracellular parasites, for example, microsporidia, or even highly condensed mitochondrial DNAs.
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Reviewer #2 (Public review):
Summary:
Programmed DNA elimination is increasingly recognised as an important phenomenon across many species, including in animals. Exactly how widespread is still unclear, and the function of PDE is even more mysterious in most species where it has been described. PDE has been discovered in several nematode species, and in this manuscript, the authors carry out a more extensive search for PDE. They find PDE in many species, indicating that it is widespread across the phylum.
Strengths:
The large number of species across many different clades provides good evidence that the phenomenon has evolved many times independently. The work will therefore prompt many further studies characterising individual species, and potentially linking the evolution of the phenomenon to other features of these species' …
Reviewer #2 (Public review):
Summary:
Programmed DNA elimination is increasingly recognised as an important phenomenon across many species, including in animals. Exactly how widespread is still unclear, and the function of PDE is even more mysterious in most species where it has been described. PDE has been discovered in several nematode species, and in this manuscript, the authors carry out a more extensive search for PDE. They find PDE in many species, indicating that it is widespread across the phylum.
Strengths:
The large number of species across many different clades provides good evidence that the phenomenon has evolved many times independently. The work will therefore prompt many further studies characterising individual species, and potentially linking the evolution of the phenomenon to other features of these species' ecological characteristics.
Weaknesses:
The major technical weakness of this project is the assay that is used to evaluate PDE. First, this assay is clearly insensitive, as the authors acknowledge, O. tipulae, which has PDE, does not appear in their screen. Second, the assay gives no information about breakpoints and only limited, non-quantitative information about how much DNA is eliminated. Thus, their data really is only a preliminary screen, which would need to be confirmed by genomic assays.
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Reviewer #3 (Public review):
Summary:
Somatic programmed DNA elimination (PDE), also known as chromatin diminution, has primarily been studied in parasitic nematodes, such as Ascaris species, in which it was discovered almost 140 years ago. Recently, PDE has also been reported in three non-parasitic nematode species. In this manuscript, Launay et al present the results of a large-scale cytological and evolutionary study of PDE across 29 free-living nematode species belonging to the Rhabditidae family, for which they established a phylogeny based on 18S and 28S ribosomal RNA sequences. By combining DNA staining and telomere DNA FISH labeling in developing embryos, they convincingly document the formation of lagging fragments and/or the loss of long germline telomeres in 17 species, during one particular division of somatic precursor cells.
Reviewer #3 (Public review):
Summary:
Somatic programmed DNA elimination (PDE), also known as chromatin diminution, has primarily been studied in parasitic nematodes, such as Ascaris species, in which it was discovered almost 140 years ago. Recently, PDE has also been reported in three non-parasitic nematode species. In this manuscript, Launay et al present the results of a large-scale cytological and evolutionary study of PDE across 29 free-living nematode species belonging to the Rhabditidae family, for which they established a phylogeny based on 18S and 28S ribosomal RNA sequences. By combining DNA staining and telomere DNA FISH labeling in developing embryos, they convincingly document the formation of lagging fragments and/or the loss of long germline telomeres in 17 species, during one particular division of somatic precursor cells.
Strengths:
(1) The whole study is well executed, and the results are convincing.
(2) The authors present compelling evidence that PDE is an ancestral feature of Rhabditidae nematodes.
(3) This study provides a valuable resource of lab-tractable species for future PDE studies.
Weaknesses:
(1) Some clarifications are necessary to make the figures more reader-friendly.
(2) Important references to ciliates are missing.
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Author response:
We thank you and the three reviewers for their careful examination and critical assessment of our work.
All acknowledge the significance of revealing the widespread occurrence of programmed DNA elimination (PDE) in nematodes, a phenomenon long considered a parasitic specificity. The reviewers, particularly Reviewer #2 and the Editors, have raised important concerns regarding confirming PDE with more sensitive methods, in particular using genomic data to characterize breaksite motifs across the phylogeny and to better understand the amount and nature of eliminated sequences across species. While we fully agree that such confirmation would ideally complement our discovery, this approach extends beyond the scope of the current manuscript. Our primary aim was to inform the scientific community of the widespread occurrence …
Author response:
We thank you and the three reviewers for their careful examination and critical assessment of our work.
All acknowledge the significance of revealing the widespread occurrence of programmed DNA elimination (PDE) in nematodes, a phenomenon long considered a parasitic specificity. The reviewers, particularly Reviewer #2 and the Editors, have raised important concerns regarding confirming PDE with more sensitive methods, in particular using genomic data to characterize breaksite motifs across the phylogeny and to better understand the amount and nature of eliminated sequences across species. While we fully agree that such confirmation would ideally complement our discovery, this approach extends beyond the scope of the current manuscript. Our primary aim was to inform the scientific community of the widespread occurrence of PDE in the short term.
In the longer term, an ambitious collaborative effort is currently underway to produce high-quality genome assemblies of several 100s of nematode species (ENA: PRJEB36817) , covering the diversity of Rhabditina and beyond. These will enable precisely characterising PDE, ultimately addressing these concerns. However, given the scale of this project, aiming at telomere-to-telomere assemblies - which can be particularly challenging for species that perform PDE - it will take considerable time. We believe the community should be informed of the widespread nature of PDE now, rather than waiting for this genomic data.
Nevertheless, we would like to emphasize that PDE has already been confirmed using genomics in the three clades where we have identified it cytologically: through our own work in Mesorhabditis (1) and Letcher et al., in prep, and also in Caenorhabditis (2) and Oscheius (3, 4). We will state this explicitly in our revision.
For these reasons, and to avoid overstepping extensive genomic studies that are underway, we will maintain our focus on the cytological description in this manuscript.
In addition to the above-mentioned concern, we will also address the other points:
Reviewer #1:
“Although most PDE claims are supported by solid evidence, some of the existing data do not describe the depth of characterization, e.g., how many replicates were conducted for each species? How reproducible are the claimed PDEs between embryos in terms of timing and cell identities destined for PDE? Is it possible to validate a subset of PDE with independent evidence, especially for those with marginal PDE? This is important because some dying embryos may fail to maintain their chromosome integrity and release some of the broken DNA, some others may suffer from noise such as intracellular parasites, for example, microsporidia, or even highly condensed mitochondrial DNA.
we will provide the missing information concerning number of observed embryos (using DNA stainings or DNA-FISH), and better explain and illustrate the reason why the observed fragments cannot be attributed to intracellular parasites, or to the consequence of dying embryos.
Reviewer #3:
Some clarifications are necessary to make the figures more reader-friendly.
This will be improved, thank you for pointing this out
Important references to ciliates are missing.
Thank you for pointing this out. We will improve the comparisons that can be made with the mechanism of PDE found in ciliates.
References
(1) C. Rey, C. Launay, E. Wenger, M. Delattre, Programmed DNA elimination in Mesorhabditis nematodes. Curr Biol 33, 3711-3721.e5 (2023).
(2) L. Stevens, S. Sun, N. Haruta, L. Xiao, N. Uwatoko, M. Kieninger, K. Sato, A. Yoshida, D. Absolon, J. Collins, A. Sugimoto, T. Kikuchi, M. Blaxter, Programmed DNA elimination was present in the last common ancestor of Caenorhabditis nematodes. bioRxiv [Preprint] (2025). https://doi.org/10.1101/2025.10.23.681605.
(3) T. C. Dockendorff, B. Estrem, J. Reed, J. R. Simmons, S. B. Zadegan, M. V. Zagoskin, V. Terta, E. Villalobos, E. M. Seaberry, J. Wang, The nematode Oscheius tipulae as a genetic model for programmed DNA elimination. Curr Biol 32, 5083-5098.e6 (2022).
(4) P. M. Gonzalez de la Rosa, M. Thomson, U. Trivedi, A. Tracey, S. Tandonnet, M. Blaxter, A telomere-to-telomere assembly of Oscheius tipulae and the evolution of rhabditid nematode chromosomes. G3 (Bethesda) 11, jkaa020 (2021).
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