Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2000 May 15;191(10):1631-6.
doi: 10.1084/jem.191.10.1631.

The old and the restless

S M Lewis  1 , G E Wu
Affiliations
Review

The old and the restless

S M Lewis et al. J Exp Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
RAG-mediated rearrangement. (A) V(D)J recombination involves site-specific recognition and cleavage of a 12- and 23-spacer RSS (filled and open triangles). The steps that directly involve RAG-1 and RAG-2 are indicated by the gray ovals. These include strand cleavage and possibly some coding end processing. The gray ovals are not intended to specify actual protein position or size. The rejoining of the broken ends is achieved by other DNA repair functions. (i) The usual outcome is a signal joint (at most loci, this product is excised by recombination) and a coding joint. Mostly characteristic of the coding joint product, base loss and additions are also sometimes seen at signal joints. (ii) A less common outcome of V(D)J recombination is hybrid joint formation, where the RSS are exchanged between coding ends. This type of joint also exhibits base loss and addition. (B) RAG-mediated transposition involves site-specific recognition and cleavage of a 12- and 23-spacer RSS, followed by attachment of the RSS 3′ ends to a staggered break introduced at a nonspecific target site. Fill-in synthesis of the staggered break completes the formation of a 5-bp target site duplication, and this, along with the resealing of DNA ends, remaining at the exit site, presumably could be carried out by non-RAG functions. RAG-mediated transposition has not yet been observed in vivo.
Figure 2
Figure 2
Postulated intermediates in the molecular evolution of the Ig and TCR loci. (A) One theory is that the event responsible for the existence of the modular recombination units characterizing today's Ig and TCR loci was a singularity that took place early in vertebrate evolution. With the integration of a mobile element, an ancient gene encoding an Ig superfamily domain was split into two parts. The mobile element imported RAG recombinase, its RSS, and possibly other element-related features, into the vertebrate genome. Reassembly of a functional exon required site-specific excision of the introduced mobile element, through a RAG-mediated recombination event targeting the RSS motifs. (B) After the RAG transposon integrated, the interrupted gene was duplicated. It has been suggested by Litman et al. (reference 2) that the presence of clustered arrays of duplicated genes, as found today in sharks, resembles an early locus configuration. On this view, V(D)J recombination activity in germline tissues could have led to the following derived features: (i) joined copies, as seen in cartilaginous fish, arose through a “standard” V(D)J joining event resulting in coding joint formation; (ii) the de novo creation of D segments could have arisen from intercluster recombinations resulting in the formation of signal joints with junctional insertions; (iii) the substitution of a 12-spacer RSS for a 23-spacer RSS or vice versa may have resulted from the “hybrid joint” outcome of germline joining. All of the postulated manipulations are RAG mediated and site specific. Events shown in i and iii are supported by evidence from sharks. MYA, million years ago.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Marchalonis J.J., Schluter S.F., Bernstein R.M., Shen S., Edmundson A.B. Phylogenetic emergence and molecular evolution of the immunoglobulin family. Adv. Immunol. 1998;70:417–506. - PubMed
    1. Litman G.W., Anderson M.K., Rast J.P. Evolution of antigen binding receptors. Annu. Rev. Immunol. 1999;17:109–147. - PubMed
    1. Sakano H., Huppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979;280:288–294. - PubMed
    1. Oettinger M.A., Schatz D.G., Gorka C., Baltimore D. Rag-1 and Rag-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248:1517–1523. - PubMed
    1. van Gent D.C., Mizuuchi D., Gellert M. Similarities between initiation of V(D)J recombination and retroviral integration. Science. 1996;271:1592–1594. - PubMed

Publication types