Mammalian transposable elements and their impacts on genome evolution

Transposable elements (TEs) are genetic elements with the ability to mobilize and replicate themselves in a genome. Mammalian genomes are dominated by TEs, which can reach copy numbers in the hundreds of thousands. As a result, TEs have had significant impacts on mammalian evolution. Here we summarize the current understanding of TE content in mammal genomes and find that, with a few exceptions, most fall within a predictable range of observations. First, one third to one half of the genome is derived from TEs. Second, most mammalian genomes are dominated by LINE and SINE retrotransposons, more limited LTR retrotransposons, and minimal DNA transposon accumulation. Third, most mammal genome contains at least one family of actively accumulating retrotransposon. Finally, horizontal transfer of TEs among lineages is rare. TE exaptation events are being recognized with increasing frequency. Despite these beneficial aspects of TE content and activity, the majority of TE insertions are neutral or deleterious. To limit the deleterious effects of TE proliferation, the genome has evolved several defense mechanisms that act at the epigenetic, transcriptional, and post-transcriptional levels. The interaction between TEs and these defense mechanisms has led to an evolutionary arms race where TEs are suppressed, evolve to escape suppression, then are suppressed again as the defense mechanisms undergo compensatory change. The result is complex and constantly evolving interactions between TEs and host genomes.

[1]  H. Levin,et al.  A novel mechanism of self-primed reverse transcription defines a new family of retroelements , 1995, Molecular and cellular biology.

[2]  J. Jurka,et al.  Evolutionary history of 7SL RNA-derived SINEs in Supraprimates. , 2007, Trends in genetics : TIG.

[3]  Miriam K. Konkel,et al.  Genome analysis of the platypus reveals unique signatures of evolution , 2008, Nature.

[4]  M. Lynch,et al.  The Origins of Genome Complexity , 2003, Science.

[5]  D. A. Kramerov,et al.  CAN—a pan-carnivore SINE family , 2001, Mammalian Genome.

[6]  Keith R. Oliver,et al.  Mobile DNA and the TE-Thrust hypothesis: supporting evidence from the primates , 2011, Mobile DNA.

[7]  T. J. Robinson,et al.  Impacts of the Cretaceous Terrestrial Revolution and KPg Extinction on Mammal Diversification , 2011, Science.

[8]  D A Kramerov,et al.  Origin and evolution of SINEs in eukaryotic genomes , 2011, Heredity.

[9]  A. Nekrutenko,et al.  Transposable elements are found in a large number of human protein-coding genes. , 2001, Trends in genetics : TIG.

[10]  D. Ray,et al.  Large numbers of novel miRNAs originate from DNA transposons and are coincident with a large species radiation in bats. , 2014, Molecular biology and evolution.

[11]  A. Smit,et al.  Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences. , 1995, Journal of molecular biology.

[12]  D. Largaespada,et al.  Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system , 2005, Nature.

[13]  S. Conticello The AID/APOBEC family of nucleic acid mutators , 2008, Genome Biology.

[14]  Colin N. Dewey,et al.  Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution , 2004, Nature.

[15]  S. Boissinot,et al.  Different Rates of LINE-1 (L1) Retrotransposon Amplification and Evolution in New World Monkeys , 2003, Journal of Molecular Evolution.

[16]  E. Ostertag,et al.  Biology of mammalian L1 retrotransposons. , 2001, Annual review of genetics.

[17]  Liane Gagnier,et al.  Retroviral Elements and Their Hosts: Insertional Mutagenesis in the Mouse Germ Line , 2006, PLoS genetics.

[18]  C Zeyl,et al.  MUTATIONAL MELTDOWN IN LABORATORY YEAST POPULATIONS , 2001, Evolution; international journal of organic evolution.

[19]  D. Ray,et al.  Evolution and Diversity of Transposable Elements in Vertebrate Genomes , 2017, Genome biology and evolution.

[20]  Yutaka Suzuki,et al.  Supplemental Material Title : Long terminal repeats power evolution of genes and gene expression programs in mammalian oocytes and zygotes , 2017 .

[21]  N. Okada,et al.  Genealogy of families of SINEs in cetaceans and artiodactyls: the presence of a huge superfamily of tRNA(Glu)-derived families of SINEs. , 1999, Molecular biology and evolution.

[22]  I. Arkhipova,et al.  A widespread class of reverse transcriptase-related cellular genes , 2011, Proceedings of the National Academy of Sciences.

[23]  Rebecca J. Oakey,et al.  Transposable Elements Re-Wire and Fine-Tune the Transcriptome , 2013, PLoS genetics.

[24]  Yoichi Matsuda,et al.  Mili, a mammalian member of piwi family gene, is essential for spermatogenesis , 2004, Development.

[25]  Cédric Feschotte,et al.  Ancient Transposable Elements Transformed the Uterine Regulatory Landscape and Transcriptome during the Evolution of Mammalian Pregnancy , 2015, Cell reports.

[26]  F. Gage,et al.  The Role of Transposable Elements in Health and Diseases of the Central Nervous System , 2013, The Journal of Neuroscience.

[27]  R. Swerdlow,et al.  A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. , 2004, Medical hypotheses.

[28]  H. Wichman,et al.  SINE extinction preceded LINE extinction in sigmodontine rodents: implications for retrotranspositional dynamics and mechanisms , 2005, Cytogenetic and Genome Research.

[29]  B. Mcclintock,et al.  The significance of responses of the genome to challenge. , 1984, Science.

[30]  F. Gage,et al.  Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity , 2015, Cell.

[31]  S. Rafii,et al.  Two waves of de novo methylation during mouse germ cell development , 2014, Genes & development.

[32]  Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[33]  J. Werren Selfish genetic elements, genetic conflict, and evolutionary innovation , 2011, Proceedings of the National Academy of Sciences.

[34]  Meganathan P. Ramakodi,et al.  Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs , 2014, Science.

[35]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[36]  H. Kazazian,et al.  Roles for retrotransposon insertions in human disease , 2016, Mobile DNA.

[37]  C. Feschotte,et al.  DNA transposons and the evolution of eukaryotic genomes. , 2007, Annual review of genetics.

[38]  György Abrusán,et al.  The Distribution of L1 and Alu Retroelements in Relation to GC Content on Human Sex Chromosomes Is Consistent with the Ectopic Recombination Model , 2006, Journal of Molecular Evolution.

[39]  J. Mccoy,et al.  Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis , 2000, Nature.

[40]  M. Malim,et al.  DNA Deamination Mediates Innate Immunity to Retroviral Infection , 2003, Cell.

[41]  Josefa González,et al.  The impact of transposable elements in environmental adaptation , 2013, Molecular ecology.

[42]  Differential SINE evolution in vesper and non-vesper bats , 2015, Mobile DNA.

[43]  J. V. Moran,et al.  APOBEC3A deaminates transiently exposed single-strand DNA during LINE-1 retrotransposition , 2014, eLife.

[44]  S. Boissinot,et al.  Independent and parallel lateral transfer of DNA transposons in tetrapod genomes. , 2010, Gene.

[45]  J. V. Moran,et al.  Hot L1s account for the bulk of retrotransposition in the human population , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  A. Smit,et al.  Identification of a new, abundant superfamily of mammalian LTR-transposons. , 1993, Nucleic acids research.

[47]  D. Ray,et al.  The limited distribution of Helitrons to vesper bats supports horizontal transfer. , 2011, Gene.

[48]  K. Roemer,et al.  Physical and Functional Interactions of Human Endogenous Retrovirus Proteins Np9 and Rec with the Promyelocytic Leukemia Zinc Finger Protein , 2007, Journal of Virology.

[49]  Manfred Gessler,et al.  Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals. , 2005, Gene.

[50]  Vincent J. Lynch,et al.  Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals , 2011, Nature Genetics.

[51]  D. Ray,et al.  Transposable Element Targeting by piRNAs in Laurasiatherians with Distinct Transposable Element Histories , 2016, Genome biology and evolution.

[52]  D. Ray,et al.  Survey Sequencing Reveals Elevated DNA Transposon Activity, Novel Elements, and Variation in Repetitive Landscapes among Vesper Bats , 2012, Genome biology and evolution.

[53]  S. Masuda,et al.  A Stress-Activated Transposon in Arabidopsis Induces Transgenerational Abscisic Acid Insensitivity , 2016, Scientific Reports.

[54]  K. Worley,et al.  The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution , 2009, Science.

[55]  D. Chalopin,et al.  Evolutionary impact of transposable elements on genomic diversity and lineage-specific innovation in vertebrates , 2015, Chromosome Research.

[56]  J. Dubnau,et al.  Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders , 2012, PloS one.

[57]  M. C. Marchetto,et al.  Environmental influence on L1 retrotransposons in the adult hippocampus , 2009, Hippocampus.

[58]  G. Hannon,et al.  The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race , 2007, Science.

[59]  D. Ray,et al.  Multiple waves of recent DNA transposon activity in the bat, Myotis lucifugus. , 2008, Genome research.

[60]  Katja Nowick,et al.  Rapid sequence and expression divergence suggest selection for novel function in primate-specific KRAB-ZNF genes. , 2010, Molecular biology and evolution.

[61]  Charles Lee,et al.  Alu elements mediate MYB gene tandem duplication in human T-ALL , 2007, The Journal of experimental medicine.

[62]  V. Valente,et al.  Complex evolution of gypsy in Drosophilid species. , 2004, Molecular biology and evolution.

[63]  Helen M. Rowe,et al.  KAP1 controls endogenous retroviruses in embryonic stem cells , 2010, Nature.

[64]  C. Feschotte,et al.  Endogenous viruses: insights into viral evolution and impact on host biology , 2012, Nature Reviews Genetics.

[65]  Eric S. Lander,et al.  Sequencing the nuclear genome of the extinct woolly mammoth , 2008, Nature.

[66]  Yoichi Ishida,et al.  Transposable elements and an epigenetic basis for punctuated equilibria , 2009, BioEssays : news and reviews in molecular, cellular and developmental biology.

[67]  J. D. de Visser,et al.  MUTATIONAL MELTDOWN IN LABORATORY YEAST POPULATIONS , 2001, Evolution; international journal of organic evolution.

[68]  A. Damert,et al.  Lineage specific evolution of the VNTR composite retrotransposon central domain and its role in retrotransposition of gibbon LAVA elements , 2015, BMC Genomics.

[69]  C. Feschotte,et al.  The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage. , 2007, Genome research.

[70]  J. Jurka,et al.  Duplication, coclustering, and selection of human Alu retrotransposons. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Marlen S. Clark,et al.  Repeated horizontal transfer of a DNA transposon in mammals and other tetrapods , 2008, Proceedings of the National Academy of Sciences.

[72]  Loretta Auvil,et al.  Draft genome sequence of the Tibetan antelope , 2013, Nature Communications.

[73]  C. Biémont A Brief History of the Status of Transposable Elements: from Junk Dna to Major Players in Evolution Transposable Elements as Components of Genetic Diversity , 2022 .

[74]  D. Ray,et al.  Accurate Transposable Element Annotation Is Vital When Analyzing New Genome Assemblies , 2016, Genome biology and evolution.

[75]  A. Roses,et al.  The Alu neurodegeneration hypothesis: A primate-specific mechanism for neuronal transcription noise, mitochondrial dysfunction, and manifestation of neurodegenerative disease , 2017, Alzheimer's & Dementia.

[76]  R. Emerson,et al.  Adaptive Evolution in Zinc Finger Transcription Factors , 2009, PLoS genetics.

[77]  D. Trono,et al.  The developmental control of transposable elements and the evolution of higher species. , 2015, Annual review of cell and developmental biology.

[78]  James H. Thomas,et al.  Coevolution of retroelements and tandem zinc finger genes. , 2011, Genome research.

[79]  R. Hubley,et al.  PiggyBac-ing on a Primate Genome: Novel Elements, Recent Activity and Horizontal Transfer , 2010, Genome biology and evolution.

[80]  R. Keith Slotkin,et al.  tRNA-derived small RNAs target transposable element transcripts , 2016, bioRxiv.

[81]  T. Eickbush,et al.  Origins and Evolution of Retrotransposons , 2002 .

[82]  H. Wichman,et al.  Loss of LINE-1 Activity in the Megabats , 2008, Genetics.

[83]  V. Tarabykin,et al.  Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate , 2016, PLoS genetics.

[84]  Bronwen L. Aken,et al.  Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences , 2007, Nature.

[85]  J. Boeke,et al.  Human Transposon Tectonics , 2012, Cell.

[86]  Dr. Susumu Ohno Evolution by Gene Duplication , 1970, Springer Berlin Heidelberg.

[87]  H. Wichman,et al.  Extinction of LINE-1 activity coincident with a major mammalian radiation in rodents , 2005, Cytogenetic and Genome Research.

[88]  C. Walsh,et al.  Resolving rates of mutation in the brain using single-neuron genomics , 2016, eLife.

[89]  T. Fanning Size and structure of the highly repetitive BAM HI element in mice. , 1983, Nucleic acids research.

[90]  C. Sander,et al.  A novel class of small RNAs bind to MILI protein in mouse testes , 2006, Nature.

[91]  Cédric Feschotte,et al.  Massive amplification of rolling-circle transposons in the lineage of the bat Myotis lucifugus , 2007, Proceedings of the National Academy of Sciences.

[92]  J. Jurka,et al.  Rolling-circle transposons in eukaryotes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[93]  Ravi Sachidanandam,et al.  A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. , 2008, Molecular cell.

[94]  M. Batzer,et al.  Repetitive Elements May Comprise Over Two-Thirds of the Human Genome , 2011, PLoS genetics.

[95]  Dixie L Mager,et al.  Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. , 2003, Trends in genetics : TIG.

[96]  J. Schultz,et al.  Exonization of active mouse L1s: a driver of transcriptome evolution? , 2007, BMC Genomics.

[97]  K. Ramos,et al.  Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen. , 2006, Cancer research.

[98]  T. Eickbush,et al.  The diversity of retrotransposons and the properties of their reverse transcriptases. , 2008, Virus research.

[99]  International Human Genome Sequencing Consortium Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution , 2004 .

[100]  G. Faulkner,et al.  Transposable elements in the mammalian embryo: pioneers surviving through stealth and service , 2016, Genome Biology.

[101]  Jacob D. Jaffe,et al.  The genome of the green anole lizard and a comparative analysis with birds and mammals , 2011, Nature.

[102]  J. Goodier Restricting retrotransposons: a review , 2016, Mobile DNA.

[103]  D. Trono,et al.  KRAB zinc finger proteins , 2017, Development.

[104]  Jürgen Gadau,et al.  Transposable element islands facilitate adaptation to novel environments in an invasive species , 2014, Nature Communications.

[105]  Kateryna D Makova,et al.  The (r)evolution of SINE versus LINE distributions in primate genomes: sex chromosomes are important. , 2010, Genome research.

[106]  C. Markert,et al.  Evolution of the Gene , 1948, Nature.

[107]  B. Cullen,et al.  APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells , 2006, Nucleic acids research.

[108]  D. A. Kramerov,et al.  5S rRNA-derived and tRNA-derived SINEs in fruit bats. , 2009, Genomics.

[109]  E. Liu,et al.  Evolution of the mammalian transcription factor binding repertoire via transposable elements. , 2008, Genome research.

[110]  R. Martienssen,et al.  LTR-Retrotransposon Control by tRNA-Derived Small RNAs , 2017, Cell.

[111]  M. Shimura,et al.  All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition , 2007, Nucleic acids research.

[112]  D. A. Kramerov,et al.  Bov-B-mobilized SINEs in vertebrate genomes. , 2008, Gene.

[113]  M. Emerman,et al.  Ancient Adaptive Evolution of the Primate Antiviral DNA-Editing Enzyme APOBEC3G , 2004, PLoS biology.

[114]  M. Lynch,et al.  Mutation Accumulation and the Extinction of Small Populations , 1995, The American Naturalist.

[115]  J. Bennetzen,et al.  A unified classification system for eukaryotic transposable elements , 2007, Nature Reviews Genetics.

[116]  B. Chénais Transposable elements and human cancer: a causal relationship? , 2013, Biochimica et biophysica acta.

[117]  E. Eichler,et al.  The origins and impact of primate segmental duplications. , 2009, Trends in genetics : TIG.

[118]  Floriane Plard,et al.  Comparative Analysis of Transposable Elements Highlights Mobilome Diversity and Evolution in Vertebrates , 2015, Genome biology and evolution.

[119]  Pinpointing the vesper bat transposon revolution using the Miniopterus natalensis genome , 2016, Mobile DNA.

[120]  Meganathan P. Ramakodi,et al.  Multiple Lineages of Ancient CR1 Retroposons Shaped the Early Genome Evolution of Amniotes , 2014, Genome biology and evolution.

[121]  M. Neuberger,et al.  Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases. , 2005, Molecular biology and evolution.

[122]  Montgomery Slatkin,et al.  Excess of genomic defects in a woolly mammoth on Wrangel island , 2016, PLoS genetics.

[123]  D. Ray,et al.  Bats with hATs: evidence for recent DNA transposon activity in genus Myotis. , 2006, Molecular biology and evolution.

[124]  D. Adelson,et al.  Widespread horizontal transfer of retrotransposons , 2012, Proceedings of the National Academy of Sciences.

[125]  S. Hill,et al.  Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night , 2014, Nucleic acids research.

[126]  J. Peccoud,et al.  Massive horizontal transfer of transposable elements in insects , 2017, Proceedings of the National Academy of Sciences.

[127]  K. Vlahovicek,et al.  A Retrotransposon-Driven Dicer Isoform Directs Endogenous Small Interfering RNA Production in Mouse Oocytes , 2013, Cell.

[128]  S. Dellaporta,et al.  Molecular analysis of Ac transposition and DNA replication. , 1992, Genetics.

[129]  A. Aiyar,et al.  3 Regulation of Initiation of Reverse Transcription of Retroviruses , 1993 .

[130]  M. Malim,et al.  Cytidine Deamination of Retroviral DNA by Diverse APOBEC Proteins , 2004, Current Biology.

[131]  N. Lau,et al.  Characterization of the piRNA Complex from Rat Testes , 2006, Science.

[132]  Miriam K. Konkel,et al.  Genome analysis of the platypus reveals unique signatures of evolution , 2008, Nature.

[133]  J. Bennetzen,et al.  Do Plants Have a One-Way Ticket to Genomic Obesity? , 1997, The Plant cell.

[134]  E. Koonin,et al.  Diverse groups of plant RNA and DNA viruses share related movement proteins that may possess chaperone-like activity. , 1991, The Journal of general virology.

[135]  Jerilyn A. Walker,et al.  SVA elements: a hominid-specific retroposon family. , 2005, Journal of molecular biology.

[136]  K. Rosenbloom,et al.  Rodent evolution: back to the root. , 2010, Molecular biology and evolution.

[137]  D. Haussler,et al.  29 Mammalian Genomes Reveal Novel Exaptations of Mobile Elements for Likely Regulatory Functions in the Human Genome , 2012, PloS one.

[138]  J. Mattick,et al.  Somatic retrotransposition alters the genetic landscape of the human brain , 2011, Nature.

[139]  Gersende Caron,et al.  Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts , 2003, Nature.

[140]  L. Stubbs,et al.  Deep Vertebrate Roots for Mammalian Zinc Finger Transcription Factor Subfamilies , 2014, Genome biology and evolution.

[141]  E. Eichler,et al.  A genome-wide comparison of recent chimpanzee and human segmental duplications , 2005, Nature.

[142]  Raul Urrutia,et al.  KRAB-containing zinc-finger repressor proteins , 2003, Genome Biology.

[143]  D. Ray,et al.  A non-LTR retroelement extinction in Spermophilus tridecemlineatus. , 2012, Gene.

[144]  N. Okada,et al.  Ancient SINEs from African endemic mammals. , 2003, Molecular biology and evolution.

[145]  D. Kordis,et al.  Unusual horizontal transfer of a long interspersed nuclear element between distant vertebrate classes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[146]  G. Hannon,et al.  MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. , 2007, Developmental cell.

[147]  G. Glazko,et al.  Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase , 2007, Nature Immunology.

[148]  M. Caligiuri,et al.  The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[149]  S. Devine,et al.  A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer , 2016, Genome research.

[150]  M. Nilsson,et al.  The devil is in the details: Transposable element analysis of the Tasmanian devil genome , 2016, Mobile genetic elements.

[151]  Ying Zhang,et al.  Distributions of Transposable Elements Reveal Hazardous Zones in Mammalian Introns , 2011, PLoS Comput. Biol..

[152]  Daniel M. Stoebel,et al.  The Effect of Mobile Element IS10 on Experimental Regulatory Evolution in Escherichia coli , 2010, Molecular biology and evolution.

[153]  T. Eickbush Transposing without ends: the non-LTR retrotransposable elements. , 1992, The New biologist.

[154]  D. Finnegan,et al.  Eukaryotic transposable elements and genome evolution. , 1989, Trends in genetics : TIG.

[155]  J. Jurka,et al.  Helitrons on a roll: eukaryotic rolling-circle transposons. , 2007, Trends in genetics : TIG.

[156]  Stuart R. Dennis,et al.  Transposable elements as agents of rapid adaptation may explain the genetic paradox of invasive species , 2015, Molecular ecology.

[157]  S. Sowerby,et al.  The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia. , 1998, Human molecular genetics.

[158]  L. N. van de Lagemaat,et al.  Retroelement distributions in the human genome: variations associated with age and proximity to genes. , 2002, Genome research.

[159]  E. Kirkness,et al.  Short interspersed elements (SINEs) are a major source of canine genomic diversity. , 2005, Genome research.

[160]  A. Kato,et al.  Epigenetic Regulation of a Heat-Activated Retrotransposon in Cruciferous Vegetables , 2017 .

[161]  T. Beebee,et al.  POPULATION ON THE VERGE OF A MUTATIONAL MELTDOWN? FITNESS COSTS OF GENETIC LOAD FOR AN AMPHIBIAN IN THE WILD , 2003, Evolution; international journal of organic evolution.

[162]  P. Deininger,et al.  Heavy Metals Stimulate Human LINE-1 Retrotransposition , 2005, International journal of environmental research and public health.

[163]  G. Grimaldi,et al.  Defining the beginning and end of KpnI family segments. , 1984, The EMBO journal.

[164]  C. Feschotte,et al.  Regulatory activities of transposable elements: from conflicts to benefits , 2016, Nature Reviews Genetics.

[165]  J. Spandorfer,et al.  Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma , 1988, Nature.

[166]  G. Schumann APOBEC3 proteins: major players in intracellular defence against LINE-1-mediated retrotransposition. , 2007, Biochemical Society transactions.