Table II.11. Examples of targeted natural genetic engineering.

Example

Observed specificity (mechanism)

References

DNA import and export

Special DNA uptake signals; oriT sites for initiating conjugal transfer replication

DNA uptake signals in bacterial transformation (Smith, Gwinn et al. 1999; Wang, Goodman et al. 2002; Findlay and Redfield 2009; Maughan, Wilson et al. 2010), oriT signals in conjugative plasmids and elements (Adams, Lyras et al. 2002; Grohmann, Muth et al. 2003; Parker, Becker et al. 2005; Garcillan-Barcia, Francia et al. 2009)

Homologous recombination

Special sequences stimulating DS breaks and other biochemical events in homologous exchange

(Cromie, Hyppa et al. 2007; Bagshaw, Pitt et al. 2008; Pryce and McFarlane 2009; Steiner, Steiner et al. 2009) – Chi-like sequences (Smith 1994; Sourice, Biaudet et al. 1998; El Karoui, Biaudet et al. 1999; El Karoui, Schaeffer et al. 2000; Halpern, Chiapello et al. 2007; Dillingham and Kowalczykowski 2008); Spo11 targets and hotspots in S. cerevisiae (Fukuda, Kugou et al. 2008; Nicolas 2009; Tsai, Burt et al. 2010); M26 and other recombination hotspots in S. pombe (Smith 1994; Cromie, Hyppa et al. 2007; Pryce and McFarlane 2009; Steiner, Steiner et al. 2009); repeats in plant and animal genomes (Mezard 2006; Buard and de Massy 2007; Coop and Myers 2007; McVean 2010)

Transposon insertions at special DNA structures

Insertion at REP palindromes (transposase specificity), DNA replication forks (interaction with processivity factor)

 (Tobes and Pareja 2006);  (Jomantiene, Zhao et al. 2007);(Wolkow, DeBoy et al. 1996; Nunvar, Huckova et al.) (Peters and Craig 2000; Peters and Craig 2001) (Parks, Li et al. 2009)

IS200/IS605 family target site selection

DNA sequence homology

 (Barabas, Ronning et al. 2008; Guynet, Achard et al. 2009)

IS911 target site selection

InsAB transposase binding to specific DNA sequences; regulated by synthesis of InsA transposase without specificity

 (Rousseau, Loot et al. 2007)

Cassette replacement/conversion in antigenic variation

DNA sequence homology at cassette boundaries

(Barbour and Restrepo 2000; Brayton, Palmer et al. 2002; Palmer, Futse et al. 2006; Palmer and Brayton 2007; Palmer, Bankhead et al. 2009)

Site-specific recombination (phase variation, antigenic variation, insertions and excisions)

Protein recognition of DNA sequence; protein-protein interaction

 (Nash 1981), (Silverman, Zieg et al. 1979; Komano, Kim et al. 1994; Komano 1999)

 Diversity-generating retroelements

Localized mutagenesis at duplicated segment of coding region; reverse transcription, RNA-DNA sequence homology

(Medhekar and Miller 2007; Guo, Tse et al. 2008)

Mating type cassette switching (S. cerevisiae, S. pombe, Kluyveromyces lactis)

Protein recognition of DNA sequence (endonuclease or transposase cleavage at unique site), DNA sequence homology at cassette boundaries

(Haber 1998; Klar, Ivanova et al. 1998; Dalgaard and Klar 1999; Haber 2006; Klar 2007; Barsoum, Martinez et al. 2010); (Rusche and Rine 2010)

Hermes transposon in S. cerevisiae

Preferential insertion in nucleosome-free regions

(Gangadharan, Mularoni et al. 2010)

Immune system V(D)J joining

Cleavage at specific recombination signal sequences (recognition of RSSs by RAG1+2 transposase); flexible joining by non-homologous end joining (NHEJ) functions

 (Bassing, Swat et al. 2002; Gellert 2002)

Immune system somatic hypermutation

5’ exons of immunoglobulin sequences (transcriptional specificity determinants), DIVAC element to suppress repair

 (Kinoshita and Honjo 2001; Inlay, Gao et al. 2006; Yang, Fugmann et al. 2006; Xiang and Garrard 2008; Blagodatski, Batrak et al. 2009)

Immune system class switching

Lymphokine-controlled choice of switch region transcription (promoter activation)

 (Kinoshita and Honjo 2001; Honjo, Kinoshita et al. 2002)

Budding yeast (S. cerevisaea) retroviral-like elements Ty1-Ty4

Strong preference for insertion upstream of RNA polymerase III initiation sites (protein-protein interaction of integrase with RNA polymerase III factors TFIIIB and TFIIIC).

 (Kirchner, Connolly et al. 1995; Kim, Vanguri et al. 1998; Bushman 2003; Bachman, Gelbart et al. 2005; Mou, Kenny et al. 2006)

Budding yeast retroviral-like element Ty1

Preference for insertion upstream of RNA polymerase II initiation sites rather than exons.

 (Eibel and Philippsen 1984)

Budding yeast retroviral-like element Ty5

Strong preference for insertion in transcriptionally silenced regions of the yeast genome (protein-protein interaction of integrase targeting domain (TD) with Sir4 silencing protein). Regulated in response to stress by modulation of integrase TD protein phosphorylation.

 (Zou, Ke et al. 1996; Gai and Voytas 1998; Zhu, Zou et al. 1998; Xie, Gai et al. 2001; Bushman 2003; Zhu, Dai et al. 2003; Brady, Schmidt et al. 2008); (Dai, Xie et al. 2007)

Fission yeast (S. pombe) retroviral-like elements Tf1 & Tf2

Insertion almost exclusively in intergenic regions (>98% for Tf1); biased towards PolII promoter-proximal sites, 100 – 400 bp upstream of the translation start by protein-protein interaction with transcription activators; prefers chromosome 3.

(Behrens, Hayles et al. 2000; Singleton and Levin 2002; Bowen, Jordan et al. 2003); (Bushman 2003; Kordis 2005; Leem, Ripmaster et al. 2008); (Chatterjee, Leem et al. 2009) (Novikova 2009) (Guo and Levin 2010)

MAGGY (fungal Ty3/gypsy family) retrotransposon

Targeting to heterochromatin by chromodomain in integrase protein

 (Gao, Hou et al. 2008)

Dictyostelium discoideum non-LTR retrotransposon TRE5-A

Insertion upstream of tRNA sequences by protein-protein interactions with RNA Pol III transcription factors

 (Siol, Boutliliss et al. 2006; Chung, Siol et al. 2007)

Rapidly expanding mPing transposons in rice

Insertion upstream of coding sequences

 (Naito, Zhang et al. 2009)

Drosophila ZAM LTR retrotransposons

Site-specific insertions by protein-DNA recognition

 (Faye, Arnaud et al. 2008)

Murine Leukemia Virus (MLV)

Preference for insertion upstream of transcription start sites in human genome; role for IN (integrase) and GAG proteins

 (Bushman 2003; Wu, Li et al. 2003; Mitchell, Beitzel et al. 2004); (Dunbar 2005; Lewinski, Yamashita et al. 2006)

HIV, SIV

Preference for insertion into actively transcribed regions of human genome; role for IN (integrase) and GAG proteins; HIV integrase interaction with LEDGF/p75 transcription factor

 (Mitchell, Beitzel et al. 2004; Ciuffi, Llano et al. 2005; Dunbar 2005; Ciuffi and Bushman 2006; Ciuffi, Diamond et al. 2006; Lewinski, Yamashita et al. 2006; Llano, Saenz et al. 2006; Botbol, Raghavendra et al. 2008; Ciuffi 2008); (Engelman and Cherepanov 2008; Desfarges and Ciuffi 2010; Levin, Rosenbluh et al. 2010)

Gammaretroviral (but not lentiviral) vectors

Insertion at transcription factor binding sites; 21% recurrence rate at hotspots

 (Cattoglio, Facchini et al. 2007; Deichmann, Hacein-Bey-Abina et al. 2007; Felice, Cattoglio et al. 2009)

Drosophila gypsy retrovirus

Site-specific insertion into Ovo locus regulatory region guided by Ovo protein binding sites

 (Labrador and Corces 2001; Labrador, Sha et al. 2008)

Drosophila P-factors

Preference for insertion into the 5’ end of transcripts

 (Spradling, Stern et al. 1995)

Drosophila P-factors

Targeting (“homing”) to regions of transcription factor function by incorporation of cognate binding site; region-specific

 (Kassis, Noll et al. 1992; Taillebourg and Dura 1999; Bender and Hudson 2000) (Fauvarque and Dura 1983; Hama, Ali et al. 1990; Kassis 2002)

HeT-A and TART retrotransposons

Insertion at Drosophila telomeres

 (Casacuberta and Pardue 2002; Casacuberta and Pardue 2003; Casacuberta and Pardue 2003; Pardue and DeBaryshe 2003)

R1 and R2 LINE element retrotransposons

Insertion in arthropod ribosomal 28S coding sequences (sequence-specific homing endonuclease)

 (Xiong, Burke et al. 1988; Xiong and Eickbush 1988; Xiong and Eickbush 1988; Burke, Malik et al. 1989)

Group I homing introns (DNA based)

Site-specific insertion into coding sequences in bacteria and eukaryotes (sequence-specific endonuclease)

 (Belfort and Perlman 1995)

Group II homing introns (RNA based)

Site-specific insertion into coding sequences in bacteria and eukaryotes (RNA recognition of DNA sequence motifs, reverse transcription)

 (Mohr, Smith et al. 2000; Karberg, Guo et al. 2001)

Group II intron retroelements

Insertion after intrinsic transcriptional terminators.

 (Robart, Seo et al. 2007)