Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells

Abstract

In a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected genes and repeats in somatic cells. Recent studies in nematodes suggest that DNA elimination removes all chromosome ends, resolves sex chromosome fusions, and may also promote the birth of novel genes. Programmed DNA elimination processes are diverse among species, suggesting DNA elimination likely has evolved multiple times in different taxa. The growing list of organisms that undergo DNA elimination indicates that DNA elimination may be more widespread than previously appreciated. These various organisms will serve as complementary and comparative models to study the function, mechanism, and evolution of programmed DNA elimination in metazoans.

The Nematode Oscheius tipulae as A Genetic Model for Programmed DNA Elimination

“…In contrast, programmed DNA elimination (PDE) is a dramatic form of genome change with large amounts of DNA, ranging from 0.5 to 95% of the genome, eliminated during development. [5][6][7][8][9] PDE is highly selective and reproducible and is an integral part of biology for diverse organisms.…”

“…17,18 Initial discoveries of PDE were largely dependent on careful cytological observations, and thus early models for PDE tend to have large genomes and/or discard a large amount of DNA. 5,6 With the increasing affordability of advanced sequencing technologies, whole genome sequencing has become a sensitive tool to identify PDE. 19 Genomics has been used to characterize metazoan PDE in depth, including the nature of eliminated sequences [20][21][22][23][24][25][26][27] and DNA breaks, [20][21][22] as well as the evolution of PDE.…”

“…15,16,28 A common theme emerging from these recent genomics studies is the removal of both germline-expressed genes and repetitive sequences during PDE. [5][6][7][8][9] This suggests that one function of PDE in metazoa is to permanently silence certain germline sequences potentially harmful to somatic cells. 6 PDE is also used for sex determination, 7,13,15 remodeling chromosome ends and splitting fused chromosomes, 22 and appears to be a mechanism for novel gene and chromosome evolution.…”

“…6 PDE is also used for sex determination, 7,13,15 remodeling chromosome ends and splitting fused chromosomes, 22 and appears to be a mechanism for novel gene and chromosome evolution. 6,8,9 Despite the detailed genomic and cytological descriptions of PDE in many organisms, functional and mechanistic studies of metazoan PDE are limited. 29,30 Mechanistic insights for PDE, including the contributions and roles of transposable elements and small RNAs, have primarily been gleaned from single-cell ciliates.…”

“…Thus, their underlying mechanisms may differ significantly as well. [6][7][8] Unfortunately, most metazoan models for PDE are not well suited for genetic, functional, and/or biochemical analyses. For example, in one of the best-studied organisms, the human and pig parasite Ascaris, genetic manipulation is difficult and propagation of the parasite in the pig host is expensive and not sustainable.…”