Comparative genome analysis of programmed DNA elimination in nematodes

Abstract

Programmed DNA elimination is a developmentally regulated process leading to the reproducible loss of specific genomic sequences. DNA elimination occurs in unicellular ciliates and a variety of metazoans, including invertebrates and vertebrates. In metazoa, DNA elimination typically occurs in somatic cells during early development, leaving the germline genome intact. Reference genomes for metazoa that undergo DNA elimination are not available. Here, we generated germline and somatic reference genome sequences of the DNA eliminating pig parasitic nematode and the horse parasite In addition, we carried out in-depth analyses of DNA elimination in the parasitic nematode of humans, and the parasitic nematode of dogs,s. Our analysis of nematode DNA elimination reveals that in all species, repetitive sequences (that differ among the genera) and germline-expressed genes (approximately 1000-2000 or 5%-10% of the genes) are eliminated. Thirty-five percent of these eliminated genes are conserved among these nematodes, defining a core set of eliminated genes that are preferentially expressed during spermatogenesis. Our analysis supports the view that DNA elimination in nematodes silences germline-expressed genes. Over half of the chromosome break sites are conserved between and, whereas only 10% are conserved in the more divergent Analysis of the chromosomal breakage regions suggests a sequence-independent mechanism for DNA breakage followed by telomere healing, with the formation of more accessible chromatin in the break regions prior to DNA elimination. Our genome assemblies and annotations also provide comprehensive resources for analysis of DNA elimination, parasitology research, and comparative nematode genome and epigenome studies.

Comprehensive Chromosome End Remodeling During Programmed DNA Elimination

“…The elimination only occurs in somatic cells and leads to a distinct and reduced somatic cell genome compared to the germline cell genome. This form of DNA elimination occurs in some parasitic nematodes (ascarids), copepods, ratfish, hagfish, and lampreys [4,[8][9][10][11][12][13][14][15][16]. Programmed DNA rearrangements also occur in ciliates distinguishing the germline from somatic nuclei [17][18][19][20][21].…”

“…Programmed DNA elimination in ascarid parasitic nematodes results in the loss of 13-90% of the germline DNA in forming the somatic genome [16,22]. The majority of eliminated DNA are repetitive sequences organized in tandem repeats that differ in the three genera examined (Ascaris suum = 120 bp repeat, Parascaris univalens = 5 and 10 bp repeats, and Toxocara canis = 49 bp repeat).…”

“…Comparison of the conservation of eliminated genes among these three nematodes indicates that the genes are expressed predominantly during spermatogenesis. We have proposed that DNA elimination in nematodes is a mechanism for silencing germline expressed genes [16,22]. Instead of using epigenetic mechanisms to silence germline genes in somatic cells, these genes are silenced by their elimination from the genome.…”

Deep evolutionary origin of nematode SL2 trans-splicing revealed by genome-wide analysis of the Trichinella spiralis transcriptome

“…Since our approach discards bona-fide spliced leader-containing reads that have shorter matches than 8 bp, these figures are underestimates. Nevertheless, it is clear that the proportion of genes that generate mRNAs subject to SL trans-splicing is considerably smaller in T. spiralis compared to the 80 -90% reported for other nematodes (Wang et al 2017;Sinha et al 2014;Allen et al 2011;Tourasse et al 2017).…”

“…Operons and spliced leader trans-splicing are conserved features of nematode genomes (Wang et al 2017;Pettitt et al 2014;Blumenthal 2012). Spliced leader trans-splicing is essential for the processing and expression of mRNAs derived from downstream operonic genes.…”