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  • Review Article
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Mobile elements and the human genome

Nature Reviews Genetics volume 1, pages 134–144 (2000)Cite this article

Genomic DNA is often thought of as the stable template of heredity, largely dormant and unchanging, apart from perhaps the occasional point mutation. But it has become increasingly clear that DNA is dynamic rather than static, being subjected to rearrangements, insertions and deletions. Much of this plasticity can be attributed to transposable elements and their genomic relatives.

Key Points

  • Transposable elements can be divided into two broad classes: DNA transposons and retrotransposons, according to their mechanism of action.

  • Transposable elements can also be thought of in terms of their degree of mechanistic self-sufficiency, ranging from 'autonomous' transposons (for example, L1 retrotransposons) to passenger-like sequences that are incapable of self-mobilization (for example, Alu elements).

  • It is estimated that 42% of the mass of the human genome consists of transposable element sequences. L1 sequences alone comprise 15–17% of the mass human DNA.

  • Nearly all transposon sequences in the human genome are non-functional and immobile, prompting the term 'junk' DNA. One exception to this is the L1 retrotransposon, of which there are roughly 40–60 active copies per diploid genome.

  • Transposons and transposon sequences can contribute to genome plasticity through various mechanisms, including insertion, transduction of 3′ flanking sequences and recombination.

  • The human genome may have co-opted transposable element functions for important functions such as immune defence (for example, V(D)J recombination).

  • Telomerase is an enzyme that maintains chromosome ends and may have its origins in the reverse transcriptase of a non-LTR retrotransposon.

  • Self-splicing group II introns may have given rise to modern-day spliceosomal introns.

  • Various mechanisms could function to protect the genome from excessive transposon and retrotransposon activity. These include: methylation, RNA interference, co-suppression and restricted developmental or tissue-specific expression.

  • Transposons can be used in phylogenetic studies and as reagents in molecular biology.

  • Transposons may ultimately be applied to gene delivery and insertional mutagenesis in vivo.

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Figure 1: Structures of transposable element types.
Figure 2: Target-primed reverse transcription (TPRT).
Figure 3: Transposon genome-shaping pathways.
Figure 4: V(D)J recombination.
Figure 5: Retrohoming.

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Acknowledgements

We are very grateful to the reviewers and to J. Mayer, J. Moran, M. Carmen Seleme and E. Ostertag for their thoughtful comments on the manuscript. E.L.P. is supported by a grant from the National Cancer Institute and H.H.K. is supported by grants from the NIH.

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Authors and Affiliations

  1. Department of Genetics, 475 Clinical Research Building, 415 Curie Boulevard

    Eline T. Luning Prak & Haig H. Kazazian Jr

  2. University of Pennsylvania, , Philadelphia, 19104, Pennsylvania, USA

    Eline T. Luning Prak & Haig H. Kazazian Jr

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Related links

Related links

DATABASE LINKS

copia

PRKR

factor VIII

haemophilia A

Duchenne muscular dystrophy

type 2 retinitis pigmentosa

β-thalassaemia

chronic granulomatous disease

APC

Wilms tumour suppressor gene

dystrophin

CMT

HNPP

PMP22

RAG2

RAG1

RAG2

SRY family

factor IX

CCR5

FURTHER INFORMATION

Table with human retrotransposon insertions

RepBase

Transposon DNA database at the Pasteur Institute

Infobiogen

RepeatMaker

Clustal W

GCG

BLAST

ENCYCLOPEDIA OF LIFE SCIENCES

DNA transposition: classes and mechanisms

Genome organization/ human

Developmentally programmed DNA rearrangements

Repetitive DNA: evolution

Glossary

RETROTRANSPOSITION

The process of mobilizing a retrotransposon. It involves transcription, processing of the RNA, translation, reverse transcription of the transposon RNA, and integration of the reverse transcribed DNA into a new genomic location.

LONG TERMINAL REPEATS (LTRs)

Sequences of 300–1,000 base pairs that are directly repeated at the 5′ and 3′ ends of LTR retrotransposons and retroviruses. Because of the mechanism of reverse transcription, the 5′ and 3′ LTRs of an element or retrovirus are identical on insertion into new genomic sites.

V(D)J RECOMBINATION

Site-directed DNA recombination carried out by RAG1 and RAG2 to create an enormous diversity of immunoglobulins and T-cell receptors.

TELOMERASE

A ribonucleoprotein enzyme with significant sequence similarity to reverse transcriptase of non-LTR retrotransposons. Telomerase maintains the ends of chromosomes and is expressed at increased levels in some transformed cells.

5′ TRUNCATION

Loss of the 5′ end of a retrotransposon (very common with L1 retrotransposition) upon insertion into a new genomic site.

TA SUBSET

A minor class of transcribed human L1 retrotransposons that has given rise to most cloned de novo L1 insertions.

REVERSE TRANSCRIPTASE

Enzyme used by retroviruses and retrotransposons to synthesize DNA from an RNA template.

GROUP II INTRON

A self-splicing intron of bacteria, mitochondria and chloroplasts that can excise from a specific site in a gene and insert into a specific site in another gene using activities encoded within its DNA.

INTRACISTERNAL A PARTICLE (IAP)

An LTR-containing retrotransposon of mice that resembles a retrovirus but has a defective env gene.

TRANSLATIONAL FRAMESHIFTING

Some viruses and transposable elements have sequences that can be read in more than one frame by the host cell ribosomes. Specific RNA sequences promote ribosomal slippage, facilitating the shift to a different reading frame.

PRIMER-BINDING SITE

Retroviral reverse transcriptase uses a transfer RNA primer to initiate DNA synthesis. The binding site for this tRNA is located near the 5′ end of the retroviral genome.

HOMINOIDS

A superfamily of the order Primates, comprising man and the anthropoid apes.

RECOMBINASE ACTIVATING GENE (RAG)

Encodes RAG proteins that facilitate the DNA rearrangements that result in the assembly of immunoglobulin and T-cell receptor genes from various gene segments.

PROCESSED PSEUDOGENES

Copies of the coding sequences of genes that lack promoters and introns. They contain poly A tails and are flanked by target-site duplications.

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Luning Prak, E., Kazazian, H. Mobile elements and the human genome. Nat Rev Genet 1, 134–144 (2000). https://doi.org/10.1038/35038572

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