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Genomic Instability and Mobile Genetic Elements in Regions Surrounding Two Discoidin I Genes of Dictyostelium Discoideum STEPHEN J

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Genomic Instability and Mobile Genetic Elements in Regions Surrounding Two Discoidin I Genes of Dictyostelium Discoideum STEPHEN J MOLECULAR AND CELLULAR BIOLOGY, Apr. 1984, p. 671-680 Vol. 4, No. 4 0270-7306/84/040671-10$02.00/0 Copyright C 1984, American Society for Microbiology Genomic Instability and Mobile Genetic Elements in Regions Surrounding Two Discoidin I Genes of Dictyostelium discoideum STEPHEN J. POOLEt AND RICHARD A. FIRTEL* Department of Biology, University of California, San Diego, La Jolla, California 92093 Received 29 August 1983/Accepted 22 December 1983 We have found that the genomic regions surrounding the linked discoidin I genes of various Dictyostelium discoideum strains have undergone rapid changes. Wild-type strain NC-4 has three complete discoidin I genes; its axenic derivative strain Ax-3L has duplicated a region starting -1 kilobase upstream from the two linked genes and extending for at least 8 kilobases past the genes. A separately maintained stock, strain Ax- 3K, does not have this duplication but has undergone a different rearrangement -3 kilobases farther upstream. We show that there are repeat elements in these rapidly changing regions. At least two of these elements, Tdd-2 and Tdd-3, have characteristics associated with mobile genetic elements. The Tdd-3 element is found in different locations in related strains and causes a 9- to 10-base-pair duplication of the target site DNA. The Tdd-2 and Tdd-3 elements do not cross-hybridize, but they share a 22-base-pair homology near one end. At two separate sites, the Tdd-3 element has transposed into the Tdd-2 element, directly adjacent to the 22-base-pair homology. The Tdd-3 element may use this 22-base-pair region as a preferential site of insertion. Transposable genetic elements constitute a fluid compo- sequences. In addition, we show in this paper that strain NC- nent of a number of eucaryotic genomes (31), including those 4 has three full discoidin I genes, but strain Ax-3L, the of yeasts (1), nematodes (4), and Drosophila melanogaster source of DNA for our previously published reports (20, 24), (28), and can be associated with a variety of chromosomal has duplicated a region containing the two linked discoidin I rearrangements (5, 6, 14, 25). We have been investigating genes. To reflect this we are adopting a nomenclature system chromosomal changes around the discoidin I genes of Dic- consistent with that of Devine et al. (3). To avoid confusion tyostelium discoideum. Discoidin I is a developmentally with previous reports from our laboratory (20), we designate regulated carbohydrate-binding protein encoded by a small different genes with Greek letters rather than with the capital multigene family (3, 20, 21-24). Previously we showed that a letters used by Devine et al. (3). In this system, the gene that particular strain of D. discoideum (Ax-3L) has a discrepancy we formerly designated Discl-A is now Discl-oa, the former in the number of genomic fragments hybridizing probes Discl-D gene is now Discl-1, and the Discl-C gene is now specific for 5' halves of discoidin I genes versus 3' halves Discl--y. These are the three complete genes of strain NC-4. (20). To investigate this we have been examining the organi- This strain also contains a gene fragment which we designate zation of the discoidin I genes in other strains, and in this DiscI-k,. The region containing the Discl-y, Discl-1, and paper we show that the regions around two of the discoidin I DiscI-ql genes has duplicated in strain Ax-3L, yielding the genes have undergone rapid changes, including duplications DiscI-y', DiscI-,', and Discl-gi' genes (20; this paper). Thus, and rearrangements. Within these regions are several repeti- the gene that we formerly designated Discl-B is now DiscI- tive elements whose patterns of hybridization differ among y'. The Discl-a, DiscI-, and Discl-y genes encode the different strains of D. discoideum. Two of these repeats discoidin Ia, lb, and Ic polypeptides, respectively, as desig- share many of the characteristics associated with mobile nated by Devine et al. (3). genetic elements, including a conserved structure, different D. discoideum strains. Strain Ax-3 is an axenic derivative sites of insertion among different strains, and movement. of wild-type strain NC-4 and can grow in liquid culture in the Unlike other eucaryotic transposable elements, these two D. absence of any bacteria (15, 16). Two stocks of this strain are discoideum elements do not have terminal repeats. The two used in this report. Strain Ax-3L is a stock of Ax-3 obtained elements do not cross-hybridize but do share a 22-base-pair from William F. Loomis (University of California, San (bp) region of homology near one end. One of the elements Diego, Calif.). Strain Ax-3K is a separately maintained stock appears to use this region of homology as a preferential site of Ax-3 obtained from Richard Kessin (Harvard University, of insertion and causes a 9- to 10-bp duplication of the target Boston, Mass.). Strains MF-B1, MF-B2, MF-D, MF-G, site DNA upon insertion. We suggest that the fluidity around DdK1O, and Dd-Ohio are strains newly isolated from the the discoidin I genes is caused by these mobile genetic wild type and were provided to us by David Francis (Univer- elements. sity of Delaware, Newark, Del.). These were grown under the same conditions as was strain NC-4 (12). Vegetatively MATERIALS AND METHODS growing cells were washed free of bacteria, and DNA was Genetic nomenclature. Devine et al. (3) have correlated the isolated as described previously (12). Growth of strain Ax-3 three isoelectric forms of discoidin I with three mRNA and isolation of DNA have been described previously (12). General methods. Most methods used were essentially as described in Maniatis et al. (17). Construction and screening * Corresponding author. of a strain Ax-3L genomic BamHI library in X BF101 was t Present address: Department of Biochemistry and Biophysics, done as described in Maniatis et al. (18). After identification, University of California, San Francisco, CA 94143. the BamHI insert was cloned into the vehicle pXF3, yielding 671 672 POOLE AND FIRTEL MOL. CELL. BIOL. U. Q -j y.11 L vc E z _ X v A 2 x o z < < B 2 i 0 z < < C E v11 o Z < < 10. - 72- 5.1- - 3.0- * - S 3g3313 -5£6 *;*t3; ,3w -4.6 _~ 1.8 - 1.4- go d ib ... FIG. 1. Genomic EcoRI blots of D. discoideum strains. DNA from the various strains was digested with EcoRI, separated on a 0.8% agarose gel, transferred to nitrocellulose, and hybridized with various nick-translated probes. The strains used were: MF, MF-G (strains MF- B1, MF-B2, and MF-D looked identical); K, K10; Oh, Ohio; NC, NC-4; AL, Ax-3L; AK, Ax-3K. Sizes in kb pairs are indicated. The probes used were: (A) purified insert of pcDdI8, a discoidin I cDNA clone spanning most of the discoidin I coding region (24); (B) fragment A of Fig. 2; and (C) an actin cDNA clone (pcDd actin B1) (8). pDdB14. Construction, screening, and subcloning of a strain strains recently isolated from the wild type. It is apparent Ax-3K EcoRI library in X Charon 13 was done in a similar that these strains show discoidin I hybridization patterns manner to yield pDdDiscK5.1. that differ from those of strain Ax-3L (lane AL), although Purified fragments to be used as probes were either nick there are certain bands that are conserved in size between translated or subcloned into M13mp8 of M13mp9 (19) and most of the strains. Most strains show the 1.8- and 10- labeled with the M13 hybridization probe primer from New kilobase (kb) bands of hybridization containing the DiscI-a England Biolabs, Beverly, Mass., following instructions gene. All strains have a band of hybridization at 1.4 kb and provided by the supplier. M13 strains were a gift of K. thus have the two tandemly linked Discl--y and DiscI-, genes Buckley. Southern (27) blot filters were hybridized at 37°C in in a similar arrangement (see Fig. 2). However, the remain- 50% formamide-3x SSC (lx SSC is 0.15 M NaCl plus 0.015 ing fragments which contain the front half of the DiscI-y M sodium citrate)-0.12 M sodium phosphate (pH 7.2)-10 gene and the back half of the DiscI-P gene and flanking mM EDTA-1% Sarkosyl-2x Denhardt solution (2). sequences show considerable variation in size among the DNA sequencing. DNA sequencing (26) was done with the different strains. Similar results are seen when other en- M13 sequencing kit of Bethesda Research Laboratories, zymes are used (data not shown). This variation is not Gaithersburg, Md., following the instructions provided by typical of all D. discoideum genomic sequences since the the supplier but with modifications as detailed elsewhere sequences surrounding the 17 to 20 actin genes do not exhibit (S. J. Poole and R. A. Firtel, J. Mol. Biol., in press). For a high degree of restriction site polymorphism (Fig. 1C). The regions of extremely high A+T composition, the 24-bp two linked discoidin I genes are, therefore, in a region that primer (Bethesda Research Laboratories) was used, and has an unusually high degree of strain differences. reactions were carried out at 43°C. Regions beyond homo- These differences are seen not only among the newly polymer deoxyribosyladenine or deoxyribosylthymine isolated wild-type D. discoideum strains, but also among stretches greater than -20 were difficult or impossible to related laboratory strains. Figure 1 shows Southern blots of read reliably.
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