Programmed genome elimination : why do many eukaryotes delete parts of their genome ?/ Elimination programmée du génome : pourquoi de nombreux eucaryotes suppriment-ils des parties de leur génome?

Seminar organized by Sandra Duharcourt from April 29 to May 4, 2024.

 

Participants

Yves BARRAL (Institute of Biochemistry, ETH Zürich – Zürich, Suisse), Dmitrij DEDUKH (Institute of animal physiology and genetics – Libechov, République Tchèque), Marie DELATTRE (Ecole Normale Supérieure de Lyon, CNRS UMR5239 – Lyon, France), Sandra DUHARCOURT (Institut Jacques Monod CNRS Université Paris Cité – Paris, France), Andreas HOUBEN (Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) – Stadt Seeland OT Gatersleben, Allemagne), Hanna KOKKO (University of Mainz – Mainz, Allemagne), Benjamin LOPPIN (École Nationale Supérieure de Lyon – Lyon, France), Jiri MACAS (Biology Centre, Czech Academy of Sciences – Ceske Budejovice, République Tchèque), Radka REIFOVÁ (Faculty of Science, Charles University – Prague, République Tchèque), Julien RICHARD ALBERT (Institut Jacques Monod – Paris, France), Laura ROSS (University of Edinburgh, Institute of Ecology and Evolution – Edinburgh, Royaume-Uni), Denis ROZE (CNRS, Institut des Sciences Sociales du Politique – Roscoff, France), Jeramiah SMITH (University of Kentucky – Lexington, États-Unis), Alexander SUH (Leibniz Institute for the Analysis of Biodiversity Change – Bonn, Allemagne), Jianbin WANG (The University of Tennessee, Knoxville – Knoxville, États-Unis).

 

Résumé 

Du 29 avril au 4 mai 2024, 15 scientifiques dont un jeune chercheur (Julien Richard Albert) se sont réunis à la Fondation des Treilles pour discuter de l’élimination programmée de génome. Ce phénomène, découvert pour la première fois à la fin du 19e siècle par T. Boveri chez des nématodes parasites, a été décrit au cours du siècle suivant chez plus de 100 espèces de 9 phylums, y compris des ciliés unicellulaires, des plantes et des métazoaires. Malgré sa fréquence, l’élimination programmée du génome reste peu étudiée et plusieurs questions importantes restent en suspens :

1) Quelles parties du génome sont éliminées et comment l’élimination se produit-elle ?

2) Pourquoi l’élimination du génome se produit-elle, comment évolue-t-elle et quelles en sont les conséquences évolutives ? L’atelier “élimination programmée du génome” a abordé ces questions en réunissant pour la première fois des scientifiques travaillant sur des groupes taxonomiques différents avec des approches variées (biologie moléculaire et cellulaire, cytogénétique, biologie évolutive et théorie). Le nombre réduit de participants et le style du séminaire, unique en son genre, ont permis de nombreuses discussions de haut niveau scientifique. Cette combinaison unique de scientifiques et de sujets abordés a généré de nouvelles idées. Ci-dessous sont indiqués les sujets abordés lors de cette réunion exceptionnelle.

 

Abstract

From April 29 to May 4, 2024, 15 scientists, including a young researcher (Julien Richard Albert), met at the Fondation des Treilles to discuss programmed genome elimination. This phenomenon was first discovered at the end of the 19th century by T. Boveri in parasitic nematodes and described over the following century in over 100 species from 9 phyla, including single-celled ciliates, plants and metazoans. Despite its frequency, programmed genome elimination remains little studied and several important questions remain unanswered:

1) What parts of the genome are eliminated and how does elimination occur?

2) Why does genome elimination occur, how does it evolve and what are the evolutionary consequences? The “programmed genome elimination” workshop addressed these questions, bringing together for the first-time scientists working on different taxonomic groups using a variety of approaches (molecular and cell biology, cytogenetics, evolutionary biology and theory). The small number of participants and the unique style of the seminar ensured a high level of scientific discussion. This unique combination of scientists and topics generated new ideas. Below are some of the topics discussed at this exceptional meeting.

 

Report

Genome stability is crucial to ensure the faithful transmission of the genetic information across cell division and sexual reproduction. However, a number of organisms can reproducibly eliminate specific parts of their genomes from specific cell types during development. Recent high-quality genome assemblies of non-model organisms suggest that this phenomenon may be far more widespread than anticipated and is perhaps not a genetic oddity, but instead an integral part of the lifecycle of thousands of species.

Massive and reproducible elimination of a large fraction of the germline genome occurs during the development of the somatic genome at each sexual cycle in unicellular ciliates. Sandra Duharcourt (Institut Jacques Monod, Paris, France) presented ongoing work of her laboratory that aims at elucidating the molecular mechanisms of programmed DNA elimination and understanding the possible functions associated with this massive genome reorganization in the ciliate Paramecium. She showed how newly identified players allows the specific selection of small RNAs corresponding to the eliminated sequences, which then guide the deposition of histone modifications on the eliminated regions. Julien Richard Albert (Institut Jacques Monod, Paris, France) leverages Paramecium genome assemblies to model the evolutionary forces acting on genes involved in programmed DNA elimination.

Progresses made using the nematode Parascaris, a human parasite, using state-of-the-art sequencing technologies have been discussed by Jianbin Wang (University of Tennessee, Knoxville, USA). Recently, an identical pattern of DNA elimination, whereby large portions of chromosomes are eliminated during early embryogenesis, including telomeres, has been uncovered in several free-living nematode species. Advances made with two species in particular, Oscheius tipulae (Jianbin Wang) and Mesorhabditis belari (Marie Delattre, ENS, Lyon, France) have been presented, revealing conserved as well as species-specific features in programmed DNA elimination. The identification of these genetically tractable species now opens the way to a better understanding on in programmed DNA elimination mechanism, function and evolution.

Alexander Suh (Centre for Molecular Biodiversity Research, Leibniz, Germany) presented his group’s research on the elimination of an enigmatic chromosome from the body cells of songbirds during their embryo development. DNA and RNA evidence suggests that this so-called “germline-restricted chromosome” is present in all 6,500 species of songbirds and relatives, and plays a role in embryo development and female fertility. In sharp contrast to normal avian chromosomes, Radka Reifová (Charles University, Prague, Czech Republic) shows that the passerine germline-restricted chromosome displays enormous variability in both size and gene content caused by frequent additions, duplications and deletions of sequences on this chromosome. She presented several candidate genes on the germline-restricted chromosome that may play an important role in germline specification and/or development and prevent its loss from the passerine genome.

Jeramiah Smith (University of Kentucky, USA) discussed recent results related to the evolution of germline specific chromosomes in jawless vertebrates and efforts to unravel the mechanisms of elimination in lamprey embryos.  These studies indicate that these germline chromosomes are very old and that their elimination may involve interactions between sister chromatids during early development.

Laura Ross (University of Edinburgh, UK) studies insects which systematically eliminate portions of their genomes from some of their cells during development. Many of these species are economically important pests or parasites, and found in hyper-diverse clades that make up a significant proportion of animal biodiversity. Yet we know almost nothing about why and how these critters undergo DNA elimination. At the meeting she presented work showing that germline elimination is associated with unusual meiotic spindle morphology in mealybugs, while the germline restricted chromosomes of fungus gnat flies appear to be of hybrid origin.

Jiří Macas (Institute of plant molecular biology, České Budějovice, Cech Republic) showed that the molecular mechanisms leading to the elimination of mobile elements and other types of repetitive DNA from the plant genomes represent an important force that counteracts the ongoing processes of repeat amplification. Differences in the efficiency of these mechanisms are thought to have contributed significantly to the evolution of the extraordinary diversity of plant nuclear genomes. Using the goatgrass Aegilops speltoides as a model, Andreas Houben (Leibniz Institute of Plant Genetics and Crop Plant Research, Germany) reported that eliminating supernumerary B chromosomes is a strictly controlled and root-specific process. Independent of centromere activity, B chromosomes undergo nondisjunction and anaphase lagging, leading to micronucleation and chromosome loss. Co-expression analysis revealed a candidate gene controlling the process of chromosome elimination.

Dmitrij Dedukh (Institute of Animal Physiology and Genetics, Liběchov, Cech Republic) presented how asexual hybrid vertebrates exploit programmed genome elimination during fertilization or gametogenesis for their reproduction. During gametogenesis one of the parental genomes is usually eliminated gradually via the inability of individual chromosomes to attach to the spindle during metaphase causing their nondisjunction and lagging during anaphase. Benjamin Loppin (ENS, Lyon, France) presented a recent work on the epigenetic marking of paternal chromosomes in the Drosophila germline that contributes to their stable transmission to the zygote. He also shared unpublished results on a possible male germline checkpoint that selectively eliminates spermatids with improperly packaged chromatin during spermiogenesis.

Yves Barral (ETH, Zurich, Switzerland) presented the studies of his laboratory focusing on how eukaryotes restrict the entry of exogenous DNA into cells and its incorporation in the genome.  Based on his studies in highly divergent budding and fission yeasts, he proposed the idea that the centromeres play a central role in defining chromosomes as self, enabling the subsequent recognition of non-self DNA and its elimination.

Denis Roze (Sorbonne University, Roscoff, France) gave an overview of current hypotheses to explain the evolution of paternal genome elimination and haplodiploidy. He also presented the results of a new mathematical model exploring the effects of inbreeding and deleterious mutations, showing in particular that inbreeding tends to favor the evolution of haplodiploidy, by reducing the fitness cost caused by the expression of partially recessive deleterious mutations in haploid males.

Hanna Kokko (Mainz University, Germany) presented new theoretical studies that show links between reproductive systems that look very different (asexual reproduction in some insects, male production from unfertilized eggs in ants, bees and wasps, occasional parthenogenesis in birds) but reveal an underlying common logic. Similarly, there is common logic underpinning parasite manipulations of host reproductive systems, which happens in diverse ways when bacteria or fungi infect insects and change their sex ratio.

Altogether, the work presented at the meeting shows that there are many shared features of programmed DNA elimination across distantly related clades, suggesting that the underlying cellular mechanisms are likely highly conserved. Collaboration between scientists working on programmed DNA elimination across diverse organisms is therefore key to understand it, and this meeting allowed us to connect key players in this field of research for the first time.  At the end of the week, we had a general discussion and worked for two halves days on the outline of a review that will write together. In conclusion, we felt very fortunate to meet and exchange ideas in this fantastic location. We want to thank the jury of the Fondation des Treilles for making this seminar possible, and the team at Les Treilles for taking excellent care of us.

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