Developmentally Programmed DNA Rearrangements

Abstract

Developmentally programmed DNA rearrangements are structural reorganizations of the genome that occur reproducibly during the development of a variety of organisms. In the majority of cases, programmed DNA rearrangements function to alter gene expression. However, in a few cases a putative function has yet to be ascribed to largeā€scale developmentally programmed DNA rearrangements.

Keywords: genome structure; Tetrahymena; transposition; DNA rearrangement; recombination

Figure 1.

(a) Cointegrate transposition. Single stranded cuts are made by transposase at both ends of the transposon (black, striped box) in donor DNA (black). The 3′ hydroxyl ends of the transposon are ligated to 5′‐phosphates of transposase‐cleaved target DNA. DNA replication fills single‐stranded gaps and recombination between duplicated transposon sequences separates the molecules yielding a donor site that retains the transposon and a target site that has acquired the transposon. (b) ‘Cut and paste’ transposition. Donor DNA (black) is cleaved at both ends of the transposition (striped black box) by transposase. The 3′ hydroxyl of the transposon is ligated to the transposase‐liberated 5′‐phosphate groups of the target DNA (red). The end result is a transposon inserted into target DNA and a double‐strand break (DSB) at the donor locus.

Figure 2.

V‐J joining. The product of V‐J joining is an imprecise coding joint encoding part of an immunoglobulin G (IgG) molecule, and a precisely joined signal joint that is eventually degraded. DNA‐PK, DNA‐dependent protein kinase; RSS, recombination signal sequence.

Figure 3.

Nonreciprocal gene conversion of an internal VSG gene (D) into an active telomeric expression site. The expressed VSG gene is located downstream of 76‐bp repeats and the eight expression site‐associated genes (ESAGs). The ESAGs are not affected in this case but may be by telomeric recombination and in situ switches. X, 76‐bp repeats; boxes A–E, distinct VSG genes, black stripes in A–E, conserved 3′ region.

Figure 4.

(a) Organization of DNA at the micronuclear and macronuclear loci of the ARP1 gene of Tetrahymena thermophila. The area inside the diagonal lines indicates micronucleus‐specific DNA whereas outside these lines macronuclear and micronuclear sequences are identical. The 2.9‐kb eliminated sequence between the diagonal lines is named the micronucleus‐specific element (mse2.9). The eliminated sequence is situated within the second intron of ARP1. Exons are marked by clear boxes; introns by shaded boxes. E, EcoRI; H, HindIII; X, XbaI. (b) Model of IES (internal eliminated sequence) deletion in T. thermophila. Red arrows represent DNA cleavage; green arrows indicate junctions created by IES excision. IES excision is initiated by a staggered double‐strand break produced at a site defined by properly situated adenosine residues on either strand. A one‐step transesterification reaction occurs to produce the chromosomal junction on one strand. Processing of the intermediate occurs to yield the mature junction. Reproduced with permission from Saveliev SV and Cox MM (1995) Genes and Development9: 248–255.

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Further Reading

Bassing CH, Swat W and Alt FW (2002) The mechanism and regulation of chromosomal V(D) J recombination. Cell 109 (Supplement): S45–55.

Craig N, Craigie R, Gellert M and Lambowitz A (eds) (2002) Mobile DNA II. Washington, DC: ASM Press.

Davila M, Foster S, Kelsoe G and Yang K (2001) A role for secondary V(D)J recombination in oncogenic chromosomal translocations? Advances in Cancer Research 81: 61–92.

Fillingham JS, Bruno D and Pearlman RE (2001) Cis‐acting requirements in flanking DNA for the programmed elimination of mse2.9: a common mechanism for deletion of internal eliminated sequences from the developing macronucleus of Tetrahymena thermophila. Nucleic Acids Research 29: 488–498.

Fillingham JS, Chilcoat ND, Turkewitz AP et al. (2002) Analysis of expressed sequence tags (ESTs) in the ciliated protozoan Tetrahymena thermophila. Journal of Eukaryotic Microbiology 49: 99–107.

Lewis SM (1999) Evolution of immunoglobulin and T‐cell receptor gene assembly. Annals of the New York Academy of Sciences 870: 58–67.

Meyer E and Duharcourt S (1996) Epigenetic programming of developmental genome rearrangements in ciliates. Cell 87: 9–12.

Mochizuki K, Fine NA, Fujisawa T and Gorovsky MA (2002) Analysis of a piwi‐related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell 110: 689–699.

Saveliev SV and Cox MM (2001) Product analysis illuminates the final steps of IES deletion in Tetrahymena thermophila. Embo Journal 20: 3251–3261.

Vanhamme L, Pays E, McCulloch R and Barry JD (2001) An update on antigenic variation in African trypanosomes. Trends in Parasitology 17: 338–343.

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Fillingham, Jeffrey S, and Pearlman, Ronald E(Sep 2005) Developmentally Programmed DNA Rearrangements. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003877]