Publication of the LBMC in the journal Current Biology, on August 21, 2023. Communication of CNRS-INSB on August 30, 2023.
Some animal species systematically destroy part of their DNA in their somatic cells. Why do they do this? But how? This programmed elimination of the genome, discovered 150 years ago, remains mysterious in the absence of suitable means of study. A paper from the Laboratory of Biology and Modelling of the Cell (LBMC - CNRS/ENS de Lyon), in press and available online in the journal Current Biology, describes a group of genetically manipulable nematode species for which almost a third of the genome is eliminated, finally offering a model for studying this fascinating process.
Some species undergo programmed DNA elimination (PDE), whereby portions of the genome are systematically destroyed in somatic cells. PDE has emerged independently in several phyla, but its function is unknown. Although the mechanisms are partially solved in ciliates, PDE remains mysterious in metazoans because the study species were not yet amenable to functional approaches. We fortuitously discovered massive PDE in the free-living nematode genus Mesorhabditis, from the same family as C. elegans. As such, these species offer many experimental advantages to start elucidating the PDE mechanisms in an animal. Here, we used cytology to describe the dynamics of chromosome fragmentation and destruction in early embryos. Elimination occurs once in development, at the third embryonic cell division in the somatic blastomeres. Chromosomes are first fragmented during S phase. Next, some of the fragments fail to align on the mitotic spindle and remain outside the re-assembled nuclei after mitosis. These fragments are gradually lost after a few cell cycles. The retained fragments form new mini chromosomes, which are properly segregated in the subsequent cell divisions. With genomic approaches, we found that Mesorhabditis mainly eliminate repeated regions and also about a hundred genes. Importantly, none of the eliminated protein-coding genes are shared between closely related Mesorhabditis species. Our results strongly suggest PDE has not been selected for regulating genes with important biological functions in Mesorhabditis but rather mainly to irreversibly remove repeated sequences in the soma. We propose that PDE may target genes, provided their elimination in the soma is invisible to selection.
illustration credits: M. Delattre