Genetic Information Research Institute, Mountain View, California
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: non-LTR retrotransposon CR1 clade ORF1p esterase PHD homeodomain
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
CR1 is one of the most abundant and widely distributed clades of non-LTR retrotransposons (Malik, Burke, and Eickbush 1999). Most CR1 elements are severely truncated at their 5' ends. Therefore, it was found only recently that they are non-LTR retrotransposons populating genomes of birds, amphibians, and fishes (Burch, Davis, and Haas 1993); lizards and turtles (Vandergon and Reitman 1994; Kajikawa, Ohshima, and Okada 1997); mammals (Smit 1996; Jurka and Kapitonov 1999a); and invertebrates (Drew and Brindley 1997).
In this paper we report new full-length CR1-like elements from zebrafish, medaka, and fruit fly. We show that ORF1-encoded proteins in various CR1-like non-LTR retrotransposons include conserved plant homeodomain (PHD) and esterase domains. Given the conservation of the PHD and esterase domains in highly divergent CR1-like retrotransposons from different species, including those split several hundred million years ago, we assume that the PHD and esterase activities of the ORF1-encoded proteins were necessary for survival of these retrotransposons. Interestingly, as for the CR1-like non-LTR retrotransposons, the life cycle of enveloped negative-stranded and positive-stranded RNA viruses in birds and mammals depends on their own esterase.
![]() |
Materials and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Using the majority rule applied to the corresponding set of multiple aligned copies of retrotransposons, we built their consensus sequences. Copies of TEs not produced directly by transpositions, such as those created by chromosomal duplications or redundant sequencing, were discarded based on the similarities between their flanking regions.
Distantly related proteins were identified using PsiBLAST (Altschul et al. 1997). Multiple alignments of protein sequences were created by CLUSTAL-W (Thompson, Higgins, and Gibson 1994). Alignments of DNA sequences were performed using the VMALN2 and PALN2 programs developed at the Genetic Information research Institute, Mountain View, California (GIRI). Phylogenetic analysis was conducted using MEGA 2.1 (Kumar et al. 2001). Protein domains described in this article were identified using the Family Pairwise Search (FPS) algorithm (Bailey and Grundy 1999; http://fps.sdsc.edu/) and the SUPERFAMILY protein assignments server (Gough et al. 2001; http://supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY/). Scoring of the protein sequences by FPS was performed against Pfam, a collection of protein family alignments reconstructed using hidden Markov models (Bateman et al. 2002). Assignment by SUPERFAMILY has been performed using SCOPE, a library of protein superfamilies (Murzin et al. 1995).
Sequences of retrotransposons reported here were deposited in the Repbase Update in the sections designated for fruit fly, zebrafish, human, vertebrates and invertebrates.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
The second family of zebrafish CR1-like elements is represented by a 4238-bp CR1-2_DR consensus sequence (fig. 1) assembled from another 10 copies that are also 98% identical to the consensus. Originally, a 600-bp fragment, 98% identical to a portion of the CR1-2_DR consensus sequence (positions 34224062), was reported as a LINE element (Okada et al. 1997). Recently, a
2900-bp CR1-2_DR copy was deposited in Repbase Update as the CR1DR2 element (Jekosch 2002), which is 98% identical to the coding region of the CR1-2_DR consensus sequence (positions 11114008). Surprisingly, the CR1-2_DR consensus sequence includes a long 1110-bp 5' UTR region corresponding to ORF1 in various CR1-like elements. The only ORF in CR1-2_DR encodes a 965-aa CR1-2_DRp protein composed of the APE and RT domains.
Finally, the 5047-bp CR1-3_DR consensus sequence was built from seven different copies; they are 95% identical with the consensus. CR1-3_DR carries ORF1 (positions 254-1801 ) and ORF2 (positions 18054717) encoding, respectively, a 516-aa CR1-3_DR1p protein and a 971-aa CR1-3_DR2p protein. As expected, CR1-3_DR2p is composed of the APE and RT domains.
CR1 Retrotransposon from Fruit Fly
A TBLASTN-based screening of CR1-like reverse transcriptases encoded by the Drosophila melanogaster genome revealed a rather abundant family of CR1-like non-LTR retrotransposons, hereafter named CR1_DM. The 4470-bp CR1_DM consensus sequence was constructed from 20 copies that were 10% divergent from one another. It contains ORF1 and ORF2 respectively encoding a 355-aa CR1_DM1p protein and a 964-aa CR1_DM2 protein (fig. 1). Approximately 100 copies of CR1_DM are present in a sequenced portion of the D. melanogaster genome that covers mainly euchromatin regions representing
70% of the genome. Multiple subfamilies of CR1_DM are present in the genome (unpublished data).
CR1 Elements from Medaka and Blood Fluke
We also characterized a full-length 4985-bp copy of a CR1-like element in the Oryzias latipes (medaka fish) genome, called CR1-1_OL (fig. 1). Its 5' and 3' boundaries (GenBank AB054295, positions 3305314) are labeled by 300-bp direct repeats composed of an 18-bp minisatellite unit. The CR1-1_OL element has been inserted into the genome relatively recently. Its ORF1 encodes a 271-aa CR1-1_OL1p protein (positions 322-1134), and ORF2 (positions 13524221) is corrupted by only two false frame shifts and one false stop codon.
Using genome survey sequences (GSS) from GenBank, we built a 3032-bp consensus sequence of the Schistosoma mansoni SR1 retrotransposon that is 700-bp longer than its sequence reported previously (Drew and Brindley 1997). The consensus sequence encodes a 950-aa SR1p protein (positions 362885) composed of the APE and RT domains. The extended region encodes APE. Available sequence data do not permit obtaining of any further 5'-extension of the SR1 consensus sequence, and we cannot prove or disprove the existence of ORF1p encoded by this element.
Diversity of the 3' Tails
Studies of DNA sequences flanking CR1-like elements presented in this article have revealed characteristics similar to those of known CR1-like elements reported previously (Haas et al. 1997; Kajikawa, Ohshima, and Okada 1997; Poulter, Butler, and Ormandy 1999). These elements do not generate target site duplications, and their 3' tails are composed of microsatellites (fig. 1). It appears that different families of CR1-elements, even those that populate the same genome, are characterized by different microsatellites that are specific for the each family. For example, the 3' termini of CR1-1_DR elements are composed of (ATTGA)n which follows GCTTGA and the polyadenylation signal. The 3' termini of CR1-2_DRs contain (AAATGT)n and they do not have any polyadenylation signal. In contrast, the 3' termini of CR1-3_DR elements are composed of the polyadenylation signal followed by (CTTGC)n.
It has not yet been proved, however, whether 3' microsatellite tails of CR1-like retrotransposons are their real termini or genomic microsatellites that served as targets during insertions of the retrotransposons. To resolve this question, we identified several CR1-like elements inserted into copies of other known TEs (unpublished data) that do not contain the microsatellites at positions targeted by the insertions. This observation suggests that the 3' microsatellites have been inserted into the genome together with CR1-like elements, and they can be considered to be distinctive hallmarks or signatures of different families. Presumably, these signatures depend on slightly different family-specific enzymatic activities encoded by the CR1-like elements. It is likely that generation of microsatellites at the 3' ends of CR1-like elements is a result of nontemplated additions by CR1-like reverse transcriptases, as shown experimentally for the I and R2 non-LTR retrotransposons (Chaboissier, Finnegan, and Bucheton 2000; Eickbush, Luan, and Eickbush 2000).
Phylogenetic Analysis
Figure 2 shows a phylogeny of ORF2p proteins encoded by CR1-like non-LTR retrotransposons and several other elements that belong to non-CR1 clades. The phylogenetic analysis strongly suggests that the CR1 clade is composed of three major subclades.
|
The PHD Domain
Computational analysis of the OFR1 proteins encoded by the zebrafish CR1-1_DR, CR1-2_DR, and CR1-3_DR elements failed to identify any zinc finger/leucine zipper motifs (ZL) similar to those present in the CR1, CR1_PS, and Maui retrotransposons from the chicken, turtle, and pufferfish genomes, respectively (Kajikawa, Ohshima, and Okada 1997; Poulter, Butler, and Ormandy 1999; Haas et al. 2001). However, ORF1p in CR1_OL from medaka fish harbors one motif distantly similar to ZL (fig. 3). Because stop codons and frame shifts that distort ORF2 encoded by the only available CR1_OL copy are present, it is likely that the originally intact ZL has also been damaged by mutations.
|
The exact function of the PHD domain is not yet known, but it is thought to be involved in proteinprotein interactions and to be of importance for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression (Aasland, Gibson, and Stewart 1995; Saha et al. 1995; Capili et al. 2001). Multiple lines of evidence suggest that PHD domain proteins can be targeted to DNA only indirectly via proteinprotein interactions (Gibbons et al. 1997; Kehle et al. 1998; Koipally et al. 1999; Lyngso et al. 2000; Yochum and Ayer 2001). Therefore, it is unlikely that the zinc fingers encoded by ORF1s in CR1-like elements are involved directly in DNA or RNA binding, as proposed earlier for the putative zinc finger/leucine zipper domains in CR1_PS (Kajikawa, Ohshima, and Okada 1997).
The Esterase Domain
On the basis of a BLASTP search, we identified only three GenBank proteins similar to CR1-3_DR1p (E < 0.01). They are the ORF1 proteins from the chicken CR1 (Haas et al. 2001), turtle CR1_PS (Kajikawa, Ohshima, and Okada 1997), and pufferfish Maui (Poulter, Butler, and Ormandy 1999) retrotransposons. Because only a central portion of CR1-3_DR1p (positions 168327) is similar to the ORF1p proteins (22% to 32% identity), we used it as a separate query for a PsiBLAST search (E < 0.005). After several iterations, the central portion converged with 150 eukaryotic and prokaryotic proteins from the esterase/acetylhydrolase superfamily (Drablos and Petersen 1997; Arpigny and Jaeger 1999). The same classification of CR1-3_DRp1 (E < 10-10) was also supported by the SUPERFAMILY genome assignments server (Gough et al. 2001). Figure 4 shows a multiple alignment of ORF1p proteins from CR1 retrotransposons and several prokaryotic and eukaryotic esterases. Two esterases included in the alignment were comprehensively studied experimentally: PAF-AH, a brain acetylhydrolase from cow (Ho et al. 1997), and RGAE, a rhamnogalacturonan acetylesterase from fungi (Molgaard, Kauppinen, and Larsen 2000). The most conserved structural hallmark of esterases is a catalytic triad composed of properly arranged serine, histidine, and aspartic acid residues (Drablos and Petersen 1997; Arpigny and Jaeger 1999; Molgaard, Kauppinen, and Larsen 2000). Different order and spacing of amino acid residues from the catalytic triad define several families of esterases (Dalrymple et al. 1997; Gough et al. 2001). Presumably, the esterase domain (ES) encoded by the CR1-like ORF1 proteins belongs to a specific family called GDSL (Arpigny and Jaeger 1999), SGNH (Molgaard, Kauppinen, and Larsen 2000), or the rhamnogalacturonan acetylesterase family (Gough et al. 2001). This family is characterized by GDS, GXND, and DXXH conserved motifs (Dalrymple et al. 1997). It has been shown experimentally (Ho et al. 1997) that serine from the first motif and aspartic acid plus histidine from the third motif belong to the catalytic triad. Strikingly, all three motifs and the catalytic triad are perfectly conserved in the highly divergent ORF1p encoded by CR1-elements from the chicken, turtle, medaka, pufferfish, and zebrafish genomes (fig. 4). The alignment also includes ES found in the ancient L3 retrotransposon fossilized in the human genome (see next section). Additionally, we found ES conserved in putative ORF1p proteins encoded by CR1-like elements fossilized in the crocodile, frog, and salmon genomes (unpublished data).
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Esterase is important for the life cycles of enveloped negative-stranded and positive-stranded RNA viruses infecting birds and mammals. For example, esterase domains are included in membrane glycoproteins, so called hemagglutinin-esterase or the HEF1 proteins, which are present on the surfaces of influenza C (Herrler et al. 1985; Rosenthal et al. 1998) and coronaviruses and toroviruses (Wurzer, Obojes, and Vlasak 2002). During the infection process, hemagglutinins interact with sialic acid molecules bound to the cell receptors. This interaction is followed by entrance into the cell of virus particles that cannot be efficient unless ester bonds formed between the hemagglutinin glycoproteins and the receptor sialic acids are cut by esterase (Herrler et al. 1985).
It is known that esterases perform enzymatic depalmitoylation of viral glycoproteins and various cellular proteins. As a result, fatty acids (usually palmitate) covalently attached to cysteines near C-termini of palmitoylated proteins are cleaved off. It is thought (Dunphy and Linder 1998) that palmitoylation can affect a protein's affinity for membranes, subcellular localization, and interactions with membrane proteins. Rhamnogalacturonan acetylesterase from fungi (RGAE, fig. 4) catalyzes degradation of polysaccharides that constitute a cell wall in the plant host (Molgaard, Kauppinen, and Larsen 2000).
The esterase domain is conserved in the highly divergent ORF1p proteins of CR1-like elements from the chicken, turtle, fish, and human genomes (and putatively from the frog and crocodile genomes). This underscores its functional importance for life cycles of CR1-like elements. Surprisingly, its function is not linked directly to any known stages of a non-LTR retrotransposon life cycle. It is really difficult to understand why the esterase was preserved by non-LTR retrotransposons whose evolution is thought to follow, usually, a "vertical transmission" model (Malik, Burke, and Eickbush 1999). However, a regular horizontal transfer/transmission of CR1-like elements would favor esterases involved in penetration of cell membranes. Interestingly, the chicken and zebrafish genomes harbor multiple CR1-like families of approximately the same age. Six of them have been identified in the chicken genome (Vandergon and Reitman 1994). Three families of CR1-like elements from the zebrafish are reported in this article. All three have been retrotransposed relatively recently because of a low 5% to 10% nucleotide divergence between elements that belong to the same family. However, there is an enormous
40% divergence between elements that belong to any of different families residing in the same genome. It is conceivable that these families have invaded the host independently, and most of their diversity was acquired in some other hosts.
The PHD domain is another specific domain that we identified in the ORF1p proteins encoded by the CR1_DM, T1, and Q non-LTR retrotransposons from fruit fly and African malaria mosquito, respectively (fig. 3). These elements form the only well-defined CR1 sub-clade whose members do not code for esterase (fig. 2). As for esterase, the PHD domain is conserved in highly divergent proteins, and its function is not related to DNA/RNA binding. The PHD domain is thought to be involved in proteinprotein interactions related to chromatin remodeling (Aasland, Gibson, and Stewart 1995; Kehle et al. 1998; Yochum and Ayer 2001). Therefore, it is possible that the PHD domain in CR1-like retrotransposons is necessary for both efficient retrotransposition and minimization of potentially harmful insertions of retrotransposons into the host genome by providing dynamic regulatory feedback between chromatin structure, expression of reverse transcriptase/endonuclease by retrotransposons, and their target-specificity. Interestingly, T1 and Q elements are most abundant in paracentromeric heterochromatin (Mukabayire and Besansky 1996). Similar abundance of different TEs in paracentromeric heterochromatin has been observed in other species (Kapitonov and Jurka 1999). It is possible that most of the TEs inserted accidentally into paracentromeric heterochromatin were fixed, whereas most of their relatives inserted originally into euchromatin have been lost. It is also possible, however, that insertion of some TEs can be channeled to heterochromatin regions by PHD-like regulatory elements, which may suppress transcription of retrotransposons at stages when most of the euchromatin is open (Jurka and Kapitonov 1999b). It is striking that some gypsy-like LTR retrotransposons have acquired "chromodomain" (Aasland and Stewart 1995; Malik and Eickbush 1999) which, like to PHD, is also involved in chromatin remodeling (Aasland, Gibson, and Stewart 1995; Aasland and Stewart 1995).
Interestingly, the PHD domain was acquired by Kaposi's sarcomaassociated herpesvirus (Coscoy, Sanchez, and Ganem 2001). The N-terminal PHD domain in MIR proteins encoded by the herpesvirus is directly involved in recruiting cellular proteins that regulate endocytosis of host immune recognition proteins (Coscoy, Sanchez, and Ganem 2001). As for the herpesvirus, CR1-like elements might have recruited the PHD domain to evade the host defense. Such evasion may be potentially important if these elements regularly trespass host cells.
One may design other interesting models employing function of PHD and ES in ORF1p proteins. However, our main goal was to identify new domains in the ORF1p proteins and to underscore the complexity of the life cycle of non-LTR retrotransposons concealed by the popular "vertical transmission" model.
![]() |
Acknowledgements |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Footnotes |
---|
![]() |
Literature Cited |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aasland, R., T. J. Gibson, and A. F. Stewart. 1995. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem. Sci 20:56-59.[CrossRef][ISI][Medline]
Aasland, R., and A. F. Stewart. 1995. The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1. Nucleic Acids Res 23:3168-3174.[Abstract]
Altschul, S. F., T. L. Madden, A. A. Schaffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman. 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389-3402.
Arpigny, J. L., and K. E. Jaeger. 1999. Bacterial lipolytic enzymes: classification and properties. Biochem. J 343:177-183.[CrossRef][ISI][Medline]
Bailey, T. L., and W. N. Grundy. 1999. Classifying proteins by family using the product of correlated p-values, pp. 1014. in P. Istrail, P. Pevzner, and M. Waterman, eds. Proceedings of the Third International Conference on Computational Molecular Biology (RECOMB99). ACM, New York.
Bateman, A., E. Birney, L. Cerruti, R. Durbin, L. Etwiller, S. R. Eddy, S. Griffiths-Jones, K. L. Howe, M. Marshall, and E. L. Sonnhammer. 2002. The Pfam protein families database. Nucleic Acids Res 30:276-280.
Berg, D. E., and M. H. Howe. 1987. Mobile DNA. American Society for Microbiology Press, Washington, DC.
Besansky, N. J. 1990. A retrotransposable element from the mosquito Anopheles gambiae. Mol. Cell. Biol 10:863-871.[ISI][Medline]
Besansky, N. J., J. A. Bedell, and O. Mukabayire. 1994. Q: a new retrotransposon from the mosquito Anopheles gambiae. Insect Mol. Biol 3:49-56.[Medline]
Burch, J. B., D. L. Davis, and N. B. Haas. 1993. Chicken repeat 1 elements contain a pol-like open reading frame and belong to the non-long terminal repeat class of retrotransposons. Proc. Natl. Acad. Sci. USA 90:8199-8203.
Capili, A. D., D. C. Schultz, I. F. Rauscher, and K. L. Borden. 2001. Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains. EMBO J 20:165-177.
Capy, P., C. Bazin, D. Higuet, and T. Langin. 1998. Dynamics and evolution of transposable elements. Chapman & Hall, New York.
Chaboissier, M. C., D. Finnegan, and A. Bucheton. 2000. Retrotransposition of the I factor, a non-long terminal repeat retrotransposon of Drosophila, generates tandem repeats at the 3' end. Nucleic Acids Res 28:2467-2472.
Coffin, J. M., S. H. Hughes, and H. E. Varmus. 1997. Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
Coscoy, L., D. J. Sanchez, and D. Ganem. 2001. A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition. J. Cell Biol 155:1265-1273.
Craig, N. L. 1995. Unity in transposition reactions. Science 270:253-254.
Dalrymple, B. P., D. H. Cybinski, I. Layton, C. S. McSweeney, G. P. Xue, Y. J. Swadling, and J. B. Lowry. 1997. Three Neocallimastix patriciarum esterases associated with the degradation of complex polysaccharides are members of a new family of hydrolases. Microbiology 143:2605-2614.[Abstract]
Dawson, A., E. Hartswood, T. Paterson, and D. J. Finnegan. 1997. A LINE-like transposable element in Drosophila, the I factor, encodes a protein with properties similar to those of retroviral nucleocapsids. EMBO J 16:4448-4455.
Drablos, F., and S. B. Petersen. 1997. Identification of conserved residues in family of esterase and lipase sequences. Methods Enzymol 284:28-61.[CrossRef][ISI][Medline]
Drew, A. C., and P. J. Brindley. 1997. A retrotransposon of the non-long terminal repeat class from the human blood fluke Schistosoma mansoni. Similarities to the chicken-repeat-1-like elements of vertebrates. Mol. Biol. Evol 14:602-610.[Abstract]
Dunphy, J. T., and M. E. Linder. 1998. Signalling functions of protein palmitoylation. Biochim. Biophys. Acta 1436:245-261.[ISI][Medline]
Eickbush, D. G., D. D. Luan, and T. H. Eickbush. 2000. Integration of Bombyx mori R2 sequences into the 28S ribosomal RNA genes of Drosophila melanogaster. Mol. Cell. Biol 20:213-223.
Gibbons, R. J., S. Bachoo, D. J. Picketts, et al 1997. Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat. Genet 17:146-148.[ISI][Medline]
Gough, J., K. Karplus, R. Hughey, and C. Chothia. 2001. Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J. Mol. Biol 313:903-919.[CrossRef][ISI][Medline]
Haas, N. B., J. M. Grabowski, J. North, J. V. Moran, H. H. Kazazian, and J. B. Burch. 2001. Subfamilies of CR1 non-LTR retrotransposons have different 5' UTR sequences but are otherwise conserved. Gene 265:175-183.[CrossRef][ISI][Medline]
Haas, N. B., J. M. Grabowski, A. B. Sivitz, and J. B. Burch. 1997. Chicken repeat 1 (CR1) elements, which define an ancient family of vertebrate non-LTR retrotransposons, contain two closely spaced open reading frames. Gene 197:305-309.[CrossRef][ISI][Medline]
Herrler, G., R. Rott, H. D. Klenk, H. P. Muller, A. K. Shukla, and R. Schauer. 1985. The receptor-destroying enzyme of influenza C virus is neuraminate-O-acetylesterase. EMBO J 4:1503-1506.[Abstract]
Ho, Y. S., L. Swenson, U. Derewenda, et al 1997. Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer. Nature 385:89-93.[CrossRef][ISI][Medline]
Hohjoh, H., and M. F. Singer. 1997. Sequence-specific single-strand RNA binding protein encoded by the human LINE-1 retrotransposon. EMBO J 16:6034-6043.
Holmes, S. E., M. F. Singer, and G. D. Swergold. 1992. Studies on p40, the leucine zipper motif-containing protein encoded by the first open reading frame of an active human LINE-1 transposable element. J. Biol. Chem 267:19765-19768.
Jekosch, K. 2002. CR1-like repeat from Danio rerio. Repbase Reports 2:7-8 (http://girinst.org/Repbase_Reports).
Jurka, J. 2000. Repbase Update: a database and an electronic journal of repetitive elements. Trends Genet 16:418-420.[CrossRef][ISI][Medline]
Jurka, J., and V. V. Kapitonov. 1999a. L3, humrep, Repbase Update (http://girinst.org/Repbase_Update).
Jurka, J., and 1999b. Sectorial mutagenesis by transposable elements. Genetica 107:239-248.[CrossRef][ISI][Medline]
Jurka, J., P. Klonowski, V. Dagman, and P. Pelton. 1996. CENSORa program for identification and elimination of repetitive elements from DNA sequences. Comput. Chem 20:119-121.[CrossRef][ISI][Medline]
Kajikawa, M., K. Ohshima, and N. Okada. 1997. Determination of the entire sequence of turtle CR1: the first open reading frame of the turtle CR1 element encodes a protein with a novel zinc finger motif. Mol. Biol. Evol 14:1206-1217.[Abstract]
Kapitonov, V. V., and J. Jurka. 1999. Molecular paleontology of transposable elements from Arabidopsis thaliana. Genetica 107:27-37.[CrossRef][ISI][Medline]
Kapitonov, V. V., and 2001. Rolling-circle transposons in eukaryotes. Proc. Natl. Acad. Sci. USA 98:8714-8719.
Kehle, J., D. Beuchle, S. Treuheit, B. Christen, J. A. Kennison, M. Bienz, and J. Muller. 1998. dMi-2, a hunchback-interacting protein that functions in polycomb repression. Science 282:1897-1900.
Koipally, J., A. Renold, J. Kim, and K. Georgopoulos. 1999. Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes. EMBO J 18:3090-3100.
Kolosha, V. O., and S. L. Martin. 1997. In vitro properties of the first ORF protein from mouse LINE-1 support its role in ribonucleoprotein particle formation during retrotransposition. Proc. Natl. Acad. Sci. USA 94:10155-10160.
Kumar, S., K. Tamura, I. B. Jakobsen, and M. Nei. 2001. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244-1245.
Lander, E. S., L. M. Linton, B. Birren, et al 2001. Initial sequencing and analysis of the human genome. Nature 409:860-921.[CrossRef][ISI][Medline]
Lovsin, N., F. Gubensek, and D. Kordi. 2001. Evolutionary dynamics in a novel L2 clade of non-LTR retrotransposons in Deuterostomia. Mol. Biol. Evol 18:2213-2224.
Lyngso, C., G. Bouteiller, C. K. Damgaard, D. Ryom, S. Sanchez-Munoz, P. L. Norby, B. J. Bonven, and P. Jorgensen. 2000. Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers. J. Biol. Chem 275:26144-26149.
Malik, H. S., W. D. Burke, and T. H. Eickbush. 1999. The age and evolution of non-LTR retrotransposable elements. Mol. Biol. Evol 16:793-805.[Abstract]
Malik, H. S., and T. H. Eickbush. 1999. Modular evolution of the integrase domain in the Ty3/Gypsy class of LTR retrotransposons. J. Virol 73:5186-5190.
Martin, S. L., and F. D. Bushman. 2001. Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon. Mol. Cell. Biol 21:467-475.
Molgaard, A., S. Kauppinen, and S. Larsen. 2000. Rhamnogalacturonan acetylesterase elucidates the structureand function of a new family of hydrolases. Structure Fold Des 8:373-383.[ISI][Medline]
Mukabayire, O., and N. J. Besansky. 1996. Distribution of T1, Q, Pegasus and mariner transposable elements on the polytene chromosomes of PEST, a standard strain of Anopheles gambiae. Chromosoma 104:585-595.[CrossRef][ISI][Medline]
Murzin, A. G., S. E. Brenner, T. Hubbard, and C. Chothia. 1995. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol 247:536-540.[CrossRef][ISI][Medline]
Okada, N., M. Hamada, I. Ogiwara, and K. Ohshima. 1997. SINEs and LINEs share common 3' sequences: a review. Gene 205:229-243.[CrossRef][ISI][Medline]
Poulter, R., M. Butler, and J. Ormandy. 1999. A LINE element from the pufferfish (fugu) Fugu rubripes which shows similarity to the CR1 family of non-LTR retrotransposons. Gene 227:169-179.[CrossRef][ISI][Medline]
Rosenthal, P. B., X. Zhang, F. Formanowski, W. Fitz, C. H. Wong, H. Meier-Ewert, J. J. Skehel, and D. C. Wiley. 1998. Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus. Nature 396:92-96.[CrossRef][ISI][Medline]
Saha, V., T. Chaplin, A. Gregorini, P. Ayton, and B. D. Young. 1995. The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. Proc. Natl. Acad. Sci. USA 92:9737-9741.
Smit, A. F. 1996. The origin of interspersed repeats in the human genome. Curr. Opin. Genet. Dev 6:743-748.[CrossRef][ISI][Medline]
Smit, A. F. 2000. L3, humrep. Repbase Update (http://girinst.org/Repbase_Update).
Smit, A. F. 2001. REX1_FURC. Repbase Update (fugrep.ref) (http://girinst.org/Repbase_Update).
Thompson, J. D., D. G. Higgins, and T. J. Gibson. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673-4680.[Abstract]
Vandergon, T. L., and M. Reitman. 1994. Evolution of chicken repeat 1 (CR1) elements: evidence for ancient subfamilies and multiple progenitors. Mol. Biol. Evol 11:886-898.[Abstract]
Volff, J. N., C. Korting, and M. Schartl. 2000. Multiple lineages of the non-LTR retrotransposon Rex1 with varying success in invading fish genomes. Mol. Biol. Evol 17:1673-1684.
Weiner, A. M. 2000. Do all SINEs lead to LINEs?. Nat. Genet 24:332-333.[CrossRef][ISI][Medline]
Wurzer, W. J., K. Obojes, and R. Vlasak. 2002. The sialate-4-O-acetylesterases of coronaviruses related to mouse hepatitis virus: a proposal to reorganize group 2 Coronaviridae. J. Gen. Virol 83:395-402.
Yochum, G. S., and D. E. Ayer. 2001. Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex. Mol. Cell. Biol 21:4110-4118.