Contribution of Transposable Elements to Human Proteins


More than half of the human genome originated in transposable elements (TEs). Although these segments are mostly located in intronic and intergenic regions, some of them can be found in protein‐coding exons. Moreover, some functionally important genes evolved from TEs. These genes are involved in major biological processes such as immunity, replication, reproduction, cell proliferation and apoptosis. In addition, TEs contribute to human proteome indirectly by retrocopying messenger ribonucleic acid (mRNA) molecules back to the genome and creating new variants of the existing genes, which in turn can evolve a new function or new expression pattern. This demonstrates the importance of TEs as a genomic pool of coding sequences for the creation and evolution of gene functions.

Key Concepts

  • More than half of the human genome originated in transposable elements and they have profound consequences for the genome evolution.
  • Transposable elements contribute to the human proteome either directly by co‐option of TE‐originated sequences or indirectly by using TE's molecular machinery to duplicate existing genetic material.
  • Retrogenes are byproducts of L1 element activity.
  • Human genes can be shuffled by the process called genome transduction that involves "leaking" transcription of a transposon.
  • Transposons moving around the genome can alter expression profile of the host genes.

Keywords: transposable elements; exaptation; human genome; molecular domestication; exonisation; gene evolution; retrogenes; alternative splicing; gene duplication

Figure 1. Structures of mobile elements present in the human genome. LTR, long terminal repeat; TSD, target site duplication; TIR, terminal inverted repeat and A and B, polymerase III internal promoters.
Figure 2. Evolutionary events leading to alternatively spliced TE cassette.
Figure 3. Simplified evolutionary history of human RNF113A gene. Shaded part of the RNF113B gene becomes an intron in one of the mRNA splicing variants.


Agrawal A, Eastman QM and Schatz DG (1998) Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394: 744–751.

Bieche I, Laurent A, Laurendeau I, et al. (2003) Placenta‐specific INSL4 expression is mediated by a human endogenous retrovirus element. Biology of Reproduction 68: 1422–1429.

Brandt J, Schrauth S, Veith AM, et al. (2005) Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon‐derived neogenes in mammals. Gene 345: 101–111.

Campillos M, Doerks T, Shah PK, et al. (2006) Computational characterization of multiple Gag‐like human proteins. Trends in Genetics 22: 585–589.

Caras IW, Davitz MA, Rhee L, et al. (1987) Cloning of decay‐accelerating factor suggests novel use of splicing to generate two proteins. Nature 325: 545–549.

Clouaire T, Roussigne M, Ecochard V, et al. (2005) The THAP domain of THAP1 is a large C2CH module with zinc‐dependent sequence‐specific DNA‐binding activity. Proceedings of the National Academy of Sciences of the United States of America 102: 6907–6912.

Finnegan DJ (1989) Eukaryotic transposable elements and genome evolution. Trends in Genetics 5: 103–107.

Force A, Lynch M, Pickett FB, et al. (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531–1545.

Gale M Jr, Blakely CM, Darveau A, et al. (2002) P52rIPK regulates the molecular cochaperone P58IPK to mediate control of the RNA‐dependent protein kinase in response to cytoplasmic stress. Biochemistry 41: 11878–11887.

Gotea V and Makalowski W (2006) Do transposable elements really contribute to proteomes? Trends in Genetics 22: 260–267.

Hayakawa T, Satta Y, Gagneux P, et al. (2001) Alu‐mediated inactivation of the human CMP‐N‐acetylneuraminic acid hydroxylase gene. Proceedings of the National Academy of Sciences of the United States of America 98: 11399–11404.

Jordan IK, Rogozin IB, Glazko GV, et al. (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends in Genetics 19: 68–72.

Kapitonov VV and Jurka J (2004) Harbinger transposons and an ancient HARBI1 gene derived from a transposase. DNA and Cell Biology 23: 311–324.

Kapitonov VV and Jurka J (2005) RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biology 3: e181.

de Koning APJ, Gu WJ, Castoe TA, et al. (2011) Repetitive elements may comprise over two‐thirds of the human genome. PLoS Genetics 7 (12): e1002384.

van de Lagemaat LN, Landry JR, Mager DL, et al. (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends in Genetics 19: 530–536.

Lin L, Jiang P, Park JW, et al. (2016) The contribution of Alu exons to the human proteome. Genome Biology 17: 15.

Liu W, Seto J, Sibille E, et al. (2003) The RNA binding domain of Jerky consists of tandemly arranged helix‐turn‐helix/homeodomain‐like motifs and binds specific sets of mRNAs. Molecular and Cellular Biology 23: 4083–4093.

Liu DX, Bischerour J, Siddique A, et al. (2007) The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase. Molecular and Cellular Biology 27: 1125–1132.

Lv BF, Shi TP, Wang XY, et al. (2006) Overexpression of the novel human gene, nuclear apoptosis‐inducing factor 1, induces apoptosis. International Journal of Biochemistry & Cell Biology 38: 671–683.

Makalowski W, Mitchell GA and Labuda D (1994) Alu sequences in the coding regions of messenger‐RNA ‐ source of protein variability. Trends in Genetics 10: 188–193.

Makalowski W (2000) Genomic scrap yard: how genomes utilize all that junk. Gene 259: 61–67.

Makalowski W (2003a) Not junk after all. Science 300: 1246–1247.

Masumoto H, Nakano M and Ohzeki J (2004) The role of CENP‐B and alpha‐satellite DNA: de novo assembly and epigenetic maintenance of human centromeres. Chromosome Research 12: 543–556.

Medstrand P, Landry JR and Mager DL (2001) Long terminal repeats are used as alternative promoters for the endothelin B receptor and apolipoprotein C‐I genes in humans. Journal of Biological Chemistry 276: 1896–1903.

Mi S, Lee X, Li XP, et al. (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403: 785–789.

Newman JC, Bailey AD, Fan HY, et al. (2008) An abundant evolutionarily conserved CSB‐PiggyBac fusion protein expressed in Cockayne syndrome. PLoS Genetics 4: e1000031.

Ono R, Nakamura K, Inoue K, et al. (2006) Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nature Genetics 38: 101–106.

Pan D and Zhang L (2009) Burst of young retrogenes and independent retrogene formation in mammals. PLoS One 4: e5040.

Pickeral OK, Makalowski W, Boguski MS, et al. (2000) Frequent human genomic DNA transduction driven by LINE‐1 retrotransposition. Genome Research 10: 411–415.

Rebollo R, Romanish MT and Mager DL (2012) Transposable elements: an abundant and natural source of regulatory sequences for host genes. Annual Review of Genetics 46: 21–42.

Sarkar A, Sim C, Hong YS, et al. (2003) Molecular evolutionary analysis of the widespread piggyBac transposon family and related “domesticated” sequences. Molecular Genetics & Genomics: MGG 270: 173–180.

Sinzelle L, Izsvak Z and Ivics Z (2009a) Molecular domestication of transposable elements: from detrimental parasites to useful host genes. Cellular and Molecular Life Sciences: CMLS 66: 1073–1093.

Sinzelle L, Kapitonov VV, Grzela DP, et al. (2008) Transposition of a reconstructed Harbinger element in human cells and functional homology with two transposon‐derived cellular genes. Proceedings of the National Academy of Sciences of the United States of America 105: 4715–4720.

Solyom S and Kazazian HH (2012) Mobile elements in the human genome: implications for disease. Genome Medicine 4 (2): 12.

Sorek R, Ast G and Graur D (2002) Alu‐containing exons are alternatively spliced. Genome Research 12: 1060–1067.

Szabo Z, Levi‐Minzi SA, Christiano AM, et al. (1999) Sequential loss of two neighboring exons of the tropoelastin gene during primate evolution. Journal of Molecular Evolution 49: 664–671.

Szczesniak MW, Ciomborowska J, Nowak W, et al. (2011) Primate and rodent specific intron gains and the origin of retrogenes with splice variants. Molecular Biology and Evolution 28: 33–37.

Thornburg BG, Gotea V and Makalowski W (2006) Transposable elements as a significant source of transcription regulating signals. Gene 365: 104–110.

Wicker T, Sabot F, Hua‐Van A, et al. (2007) A unified classification system for eukaryotic transposable elements. Nature Reviews Genetics 8: 973–982.

Xing J, Wang H, Belancio VP, et al. (2006) Emergence of primate genes by retrotransposon‐mediated sequence transduction. Proceedings of the National Academy of Sciences of the United States of America 103: 17608–17613.

Zdobnov EM, Campillos M, Harrington ED, et al. (2005) Protein coding potential of retroviruses and other transposable elements in vertebrate genomes. Nucleic Acids Research 33: 946–954.

Further Reading

Biemont C and Vieira C (2006) Genetics: junk DNA as an evolutionary force. Nature 443: 521–524.

Blaise S, de Parseval N, Benit L and Heidmann T (2003) Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proceedings of the National Academy of Sciences of the United States of America 100: 13013–13018.

Brosius J and Volff JN (2007) Modern genomes with retro‐look: retrotransposed elements, retroposition and the origin of new genes. Genome Dynamics 3: 175–190.

Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution. Science 303: 1626–1632.

Krull M, Petrusma M, Makalowski W, Brosius J and Schmitz J (2007) Functional persistence of exonized mammalian‐wide interspersed repeat elements (MIRs). Genome Research 17: 1139–1145.

Makalowski W (2003b) Not junk after all. Science 300: 1246–1247. DOI: 10.1126/science.1085690.

Maraia RJ (1995) The Impact of Short Interspersed Elements (SINEs) on the Host Genome. Austin, TX: Springer‐Verlag; R.G. Landes.

Schumann GG et al. (2010) Unique functions of repetitive transcriptomes. International Review of Cell and Molecular Biology 285: 115–188. DOI: 10.1016/B978-0-12-381047-2.00003-7.

Sinzelle L, Izsvak Z and Ivics Z (2009b) Molecular domestication of transposable elements: from detrimental parasites to useful host genes. Cellular and Molecular Life Sciences 66: 1073–1093. DOI: 10.1007/s00018-009-8376-3.

Volff JN (2006) Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes. BioEssays 28: 913–922.

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Makałowski, Wojciech, Kischka, Tabea, and Makałowska, Izabela(Apr 2017) Contribution of Transposable Elements to Human Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020793.pub2]