Programmed DNA elimination in the parasitic nematode Ascaris

Abstract

In most organisms, the whole genome is maintained throughout the life span. However, exceptions occur in some species where the genome is reduced during development through a process known as programmed DNA elimination (PDE). In the human and pig parasite Ascaris, PDE occurs during the 4 to 16 cell stages of embryogenesis, when germline chromosomes are fragmented and specific DNA sequences are reproducibly lost in all somatic cells. PDE was identified in Ascaris over 120 years ago, but little was known about its molecular details until recently. Genome sequencing revealed that approximately 1,000 germline-expressed genes are eliminated in Ascaris, suggesting PDE is a gene silencing mechanism. All germline chromosome ends are removed and remodeled during PDE. In addition, PDE increases the number of chromosomes in the somatic genome by splitting many germline chromosomes. Comparative genomics indicates that these germline chromosomes arose from fusion events. PDE separates these chromosomes at the fusion sites. These observations indicate that PDE plays a role in chromosome karyotype and evolution. Furthermore, comparative analysis of PDE in other parasitic and free-living nematodes illustrates conserved features of PDE, suggesting it has important biological significance. We summarize what is known about PDE in Ascaris and its relatives. We also discuss other potential functions, mechanisms, and the evolution of PDE in these parasites of humans and animals of veterinary importance.

Unzipped assemblies of polyploid root-knot nematode genomes reveal new kinds of unilateral composite telomeric repeats

“…Then, for each C. elegans protein of interest we retrieved the corresponding orthogroup and checked which other species were present in the same orthogroup and thus had a putative ortholog. For the specific case of telomerase we also used the Ascaris suum enzyme as a query, because strong evidence for an active telomerase in this species has been reported (Estrem and Wang, 2023).…”

End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination

“…It removes DNA from the germline genome to generate a reduced somatic genome within the life cycle of an organism. PDE occurs in single-cell ciliates (5-7) and a growing list of metazoans (8)(9)(10)(11), suggesting the PDE process likely evolved independently in distinct phylogenetic groups and confers biological function(s). There are significant variations in how PDE occurs among diverse organisms, including the developmental stages where it occurs, the amount and types of DNA eliminated, and the genomic consequences of PDE (1)(2)(3)(4).…”

“…Loss of entire chromosome(s) occurs in some arthropods, birds, lampreys, hagfish, and mammals. In the second mechanism, chromosomes are broken, and specific fragments are reproducibly retained or lost (10,12). Chromosome fragmentation requires the generation of DNA double-strand breaks (DSBs) and their subsequent healing.…”

Chromosome fusion and programmed DNA elimination shape karyotypes of parasitic nematodes

“…5 Since then, many species from diverse phylogenetic groups have been identified to undergo PDE. [1][2][3][4][6][7][8] The distinct features of PDE from each group and its sporadic presence in metazoa suggest PDE evolved independently multiple times. [1][2][3] The broad distribution of PDE further suggests it plays an important role(s) in divergent species.…”

“…However, it is unclear if the internal breaks in Ascaris autosomes also occur near the sites of chromosome fusions or if they are de novo breaks that recently arose. 2,8 The single, large (2.5 Gb) germline chromosome of Parascaris enabled early cytological analyses, making it a historical model for chromosome biology. 23,24 In addition to providing the first observation of PDE, Parascaris studies also contributed to the establishment of Sutton-Boveri chromosome theory of heredity and the understanding of meiosis, 25 centrosome function in chromosome segregation, and the biology of holocentric chromosomes.…”