Silencing of germline-expressed genes by DNA elimination in somatic cells.

Chromatin diminution is the programmed elimination of specific DNA sequences during development. It occurs in diverse species, but the function(s) of diminution and the specificity of sequence loss remain largely unknown. Diminution in the nematode Ascaris suum occurs during early embryonic cleavages and leads to the loss of germline genome sequences and the formation of a distinct genome in somatic cells. We found that ∼43 Mb (∼13%) of genome sequence is eliminated in A. suum somatic cells, including ∼12.7 Mb of unique sequence. The eliminated sequences and location of the DNA breaks are the same in all somatic lineages from a single individual and between different individuals. At least 685 genes are eliminated. These genes are preferentially expressed in the germline and during early embryogenesis. We propose that diminution is a mechanism of germline gene regulation that specifically removes a large number of genes involved in gametogenesis and early embryogenesis.

[1]  Keith Bradnam,et al.  CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes , 2007, Bioinform..

[2]  Leonard D. Goldstein,et al.  piRNAs Can Trigger a Multigenerational Epigenetic Memory in the Germline of C. elegans , 2012, Cell.

[3]  K. Moritz,et al.  Organization and dynamics of satellite and telomere DNAs in Ascaris: implications for formation and programmed breakdown of compound chromosomes , 2000, Chromosoma.

[4]  A. Streit,et al.  Genetics, Chromatin Diminution, and Sex Chromosome Evolution in the Parasitic Nematode Genus Strongyloides , 2010, Current Biology.

[5]  A. Spicher,et al.  New telomere formation after developmentally regulated chromosomal breakage during the process of chromatin diminution in ascaris lumbricoides , 1991, Cell.

[6]  L. Katz,et al.  Evolution of developmentally regulated genome rearrangements in eukaryotes. , 2005, Journal of experimental zoology. Part B, Molecular and developmental evolution.

[7]  Mario Stanke,et al.  Gene prediction with a hidden Markov model and a new intron submodel , 2003, ECCB.

[8]  Theodor Boveri.  Uber Differenzierung der Zellkerne wahrend der Furchung des Eies von Ascaris megalocephala , 1887 .

[9]  E. Eichler,et al.  Programmed loss of millions of base pairs from a vertebrate genome , 2009, Proceedings of the National Academy of Sciences.

[10]  R. Stoffel,et al.  A newly formed telomere in Ascaris suum does not exert a telomere position effect on a nearby gene , 1996, Molecular and cellular biology.

[11]  F. Müller,et al.  New telomere formation during the process of chromatin diminution in Ascaris suum. , 2002, The International journal of developmental biology.

[12]  R. Horos,et al.  Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. , 2012, Blood.

[13]  F. Müller,et al.  Chromatin diminution in nematodes , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  Lucas J. T. Kaaij,et al.  Extremely stable Piwi‐induced gene silencing in Caenorhabditis elegans , 2012, The EMBO journal.

[15]  Martin J. Simard,et al.  Function, Targets, and Evolution of Caenorhabditis elegans piRNAs , 2012, Science.

[16]  Mark Yandell,et al.  MAKER2: an annotation pipeline and genome-database management tool for second-generation genome projects , 2011, BMC Bioinformatics.

[17]  F. Müller,et al.  Chromatin diminution leads to rapid evolutionary changes in the organization of the germ line genomes of the parasitic nematodes A. suum and P. univalens. , 2004, Molecular and biochemical parasitology.

[18]  M. Kloc,et al.  Chromatin elimination--an oddity or a common mechanism in differentiation and development? , 2001, Differentiation; research in biological diversity.

[19]  F. Müller,et al.  Chromatin diminution in the parasitic nematodes ascaris suum and parascaris univalens. , 2000, International journal for parasitology.

[20]  S. Pimpinelli,et al.  Unusual kinetochores and chromatin diminution in Parascaris. , 1989, Trends in genetics : TIG.

[21]  M. R. Esteban,et al.  Chromosome elimination in sciarid flies , 2001, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  Shifeng Xue,et al.  Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning , 2011, Cell.

[23]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[24]  David Jung,et al.  Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. , 2006, Annual review of immunology.

[25]  C. Baker,et al.  Genetic Consequences of Programmed Genome Rearrangement , 2012, Current Biology.

[26]  M. Kenzelmann,et al.  Ribosomal heterogeneity from chromatin diminution in Ascaris lumbricoides. , 1994, Science.

[27]  Thomas D. Otto,et al.  RATT: Rapid Annotation Transfer Tool , 2011, Nucleic acids research.

[28]  F. Müller,et al.  Germ line — soma differentiation inAscaris: A molecular approach , 1985, Experientia.

[29]  M. Borodovsky,et al.  Gene identification in novel eukaryotic genomes by self-training algorithm , 2005, Nucleic acids research.

[30]  Weifeng Gu,et al.  C. elegans piRNAs Mediate the Genome-wide Surveillance of Germline Transcripts , 2012, Cell.

[31]  R. -. Streeck,et al.  Chromatin diminution in Ascaris suum: nucleotide sequence of the eliminated satellite DNA. , 1982, Nucleic acids research.

[32]  A. Spicher,et al.  Extremely stable transcripts may compensate for the elimination of the gene fert-1 from all Ascaris lumbricoides somatic cells. , 1994, Developmental biology.

[33]  M. Yao,et al.  DNA elimination in ciliates: transposon domestication and genome surveillance. , 2011, Annual review of genetics.

[34]  A. Weismann,et al.  The Germ-Plasm: A Theory of Heredity , 1981 .

[35]  Ian Korf,et al.  Gene finding in novel genomes , 2004, BMC Bioinformatics.

[36]  Makedonka Mitreva,et al.  Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. , 2011, Genome research.

[37]  F. Müller,et al.  Nucleotide sequence of satellite DNA contained in the eliminated genome of Ascaris lumbricoides. , 1982, Nucleic acids research.

[38]  David R. Kelley,et al.  Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks , 2012, Nature Protocols.

[39]  S. Pimpinelli,et al.  The occurrence, role and evolution of chromatin diminution in nematodes. , 1993, Parasitology today.

[40]  Theodor Boveri.  Die Entwickelung von Ascaris megalocephala mit besonderer Rücksicht auf die Kernverhältnisse , 1899 .

[41]  L. Magnenat,et al.  Developmentally Regulated Telomerase Activity Is Correlated with Chromosomal Healing during Chromatin Diminution inAscaris suum , 1999, Molecular and Cellular Biology.

[42]  María Inés Pigozzi,et al.  Heterochromatin and histone modifications in the germline-restricted chromosome of the zebra finch undergoing elimination during spermatogenesis , 2010, Chromosoma.

[43]  C. Mello,et al.  piRNAs Initiate an Epigenetic Memory of Nonself RNA in the C. elegans Germline , 2012, Cell.

[44]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[45]  S. W. Emmons,et al.  Analysis of the constancy of DNA sequences during development and evolution of the nematode Caenorhabditis elegans. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[46]  E. Birney,et al.  Velvet: algorithms for de novo short read assembly using de Bruijn graphs. , 2008, Genome research.

[47]  Paul W. Sternberg,et al.  Ascaris suum draft genome , 2011, Nature.

[48]  F. Müller,et al.  Chromatin diminution in nematode development. , 1992, Trends in genetics : TIG.

[49]  Scott Kennedy,et al.  A nuclear Argonaute promotes multi-generational epigenetic inheritance and germline immortality , 2012, Nature.