Genes embed their evolutionary history in the form of various alleles. Presence–absence variants (PAVs) are extreme cases of such alleles, where a gene present in one haplotype does not exist in another. Because PAVs may result from either birth or death of a gene, PAV genes and their alternative alleles, if available, can represent a basis for rapid intraspecific gene evolution. Using long-read sequencing technologies, this study traced the possible evolution of PAV genes in the PD1074 and CB4856 C. elegans strains as well as their alternative alleles in 14 other wild strains. We updated the CB4856 genome by filling 18 gaps and identified 46 genes and 7,460 isoforms from both strains not annotated previously. We verified 328 PAV genes, out of which 46 were C. elegans-specific. Among these possible newly born genes, 12 had alternative alleles in other wild strains; in particular, the alternative alleles of three genes showed signatures of active transposons. Alternative alleles of three other genes showed another type of signature reflected in accumulation of small insertions or deletions. Research on gene evolution using both species-specific PAV genes and their alternative alleles may provide new insights into the process of gene evolution.

Under adverse environmental conditions, nematodes arrest into dauer, an alternative developmental stage for diapause. Dauer endures unfavorable environments and interacts with host animals to access favorable environments, thus playing a critical role in survival. Here, we report that in Caenorhabditis elegans, daf-42 is essential for development into the dauer stage, as the null mutant of daf-42 exhibited a “no viable dauer” phenotype in which no viable dauers were obtained in any dauer-inducing conditions. Long-term time lapse microscopy of synchronized larvae revealed that daf-42 is involved in developmental changes from the pre-dauer L2d stage to the dauer stage. daf-42 encodes large, disordered proteins of various sizes that are expressed in and secreted from the seam cells within a narrow time window shortly before the molt into dauer stage. Transcriptome analysis showed that the transcription of genes involved in larval physiology and dauer metabolism are highly affected by the daf-42 mutation. Contrary to the notion that essential genes that control the life and death of an organism may well be conserved across diverse species, daf-42 is an evolutionarily young gene conserved only in the Caenorhabditis genus. Our study shows that dauer formation is a vital process that is controlled not only by conserved genes but also by newly emerged genes, providing important insights into evolutionary mechanisms.

Under adverse environmental conditions, nematodes arrest into dauer, an alternative developmental stage for diapause. Dauer endures unfavorable environments and interacts with host animals to access favorable environments, thus playing a critical role in survival. Here, we report that inCaenorhabditis elegans,daf-42is essential for development into the dauer stage. The null mutant of daf-42 exhibited ano viable dauer phenotype in which no viable dauers were obtained in any dauer-forming conditions while there was no obvious developmental defects outside the dauer stage. A more detailed analysis revealed thatdaf-42is involved in developmental changes from the pre-dauer L2d stage to the dauer stage.daf-42encodes large, disordered proteins of various sizes that are expressed and secreted in the seam cells within a narrow time window shortly before the molt into dauer stage. Transcriptome analysis showed that the transcription of genes involved in larval physiology and dauer metabolism are highly affected by thedaf-42 mutation. Contrary to the commonsense notion that essential genes that control the life and death of an organism are thought to be conserved factors that are present across diverse species,daf-42is an evolutionarily young gene conserved only in theCaenorhabditisgenus. Our study shows that dauer formation is a vital process that is controlled not only by conserved genes but also by newly emerged genes, providing important insights into evolutionary mechanisms.

Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how developmental stages alter synaptic transmission using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated two different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the non-dauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell non-autonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during developmental plasticity.

Telomere length must be maintained in actively dividing cells to avoid cellular arrest or death. In the absence of telomerase activity, activation of alternative lengthening of telomeres (ALT) allows the maintenance of telomeric length and prolongs the cellular lifespan. Our previous studies have established two types of ALT survivors from mouse embryonic stem cells. The key differences between these ALT survivors are telomere-constituting sequences: non-telomeric sequences and canonical telomeric repeats, with each type of ALT survivors being referred to as type I and type II, respectively. We explored how the characteristics of the two types of ALT lines reflect their fates using multi-omics approaches. The most notable gene expression signatures of type I and type II ALT cell lines were chromatin remodelling and DNA repair, respectively. Compared with type II cells, type I ALT cells accumulated more mutations and demonstrated persistent telomere instability. These findings indicate that cells of the same origin have separate routes for survival, thus providing insights into the plasticity of crisis-suffering cells and cancers.