maintenance and stability are essential, and an organism’s genome rarely
changes. Genome instability typically leads to inviability and disease.
However, examples are known where genome instability through developmentally
regulated DNA loss or rearrangements is integral in the biology of the
organism. Programmed DNA
to the loss of specific sequences from chromosomes. DNA elimination in
nematodes occurs during differentiation of the somatic lineages early in
embryonic development. In the parasitic nematode, Ascaris, we have
shown that 15% of the genome is eliminated in the somatic lineages during the
3rd through 5th cleavage (4 to 16 cell stage), while the germline genome
remains intact. Specific repetitive and unique sequences (including 1000 genes)
are lost during DNA elimination to form the somatic genome. Notably, analysis
of DNA elimination is several other parasitic nematodes demonstrates a high
fidelity of DNA elimination where the DNA breaks and sequences lost are the
same in a species. In the three nematode genera examined, repetitive sequences
(that differ among all three genera and can constitute as much as 89% of the
genome) and 1000-2000 genes (representing 5-10% of all the genes) are
eliminated. Analysis of the genes eliminated in these nematodes indicates
that they are primarily expressed in the germline and early embryo with a
core set of eliminated genes conserved in all these nematodes (35%) expressed
during spermatogenesis. Overall, these data suggest that DNA elimination in
nematodes is an extreme and irreversible mechanism for silencing a subset of
germline and early embryo expressed genes in somatic tissues and contributes to
the distinction between the germline and soma.
Studies are now underway to determine
is the mechanism of chromosome breakage? What proteins are involved?
are the breakpoints defined?
that nematodes have holocentric chromosomes (multiple centromeric/kinetochore
complexes), what determines which chromosomal regions are retained and
which are lost?
small RNAs involved in nematode programmed DNA elimination?
there discrete epigenetic changes associated with nematode DNA elimination
that chromosome breaks are healed by telomere addition, what recruits
telomerase and what factors prevent other repair mechanisms, apoptosis, or
cell cycle arrest from initiating?
are the somatic consequences of DNA elimination?
the mechanism and function of DNA elimination the same or different in the
metazoa that exhibit DNA elimination such as copepod crustaceans?
RNA Metabolism in
Ascaris as a model for nematode studies