Targeting Transposition: At Home in the Genome

The completion of the Saccharomyces genome sequence in 1996 signaled the beginning of a new chapter in repetitive element sequence analysis (Cherry et al. 1997). The genomic analysis in the article by Kim et al. (1998) in this issue provides new insights into the nature and distribution of repetitive DNA sequences in the Saccharomyces genome. It not only assesses the repetitive sequences present in the genome but also clarifies what is not found. Saccharomyces has five long terminal repeat (LTR)– retrotransposon families (Ty elements) but no nuclear LINE-like or SINE retroelements and no identifiable DNA-based transposable elements. Remarkably, each Ty family displays insertion specificity. The parallels and differences between the organization of transposable elements in the Saccharomyces genome, and what is thus far known of the organization of elements in the genomes of other eukaryotes, suggest that this chapter will have many interesting sequelae. The genomic analysis by Kim et al. (1998) further defines the relationships of the Ty families of yeast comprised of four copia-like (Ty1, Ty2, Ty4, and Ty5) and one gypsy-like (Ty3) families. The copia-like families have been divided further based on similarity of encoded proteins and LTRs. Ty1 and Ty2 share significant similarity, particularly in the capsid domain, and share a common LTR, called d. In addition, Kim et al. showed for the first time, that Ty1 and Ty2 d elements are distinct—differing consistently at a single position. Unlike retrovirus LTRs, yeast element LTRs flanking the internal domain undergo recombination, thereby deleting one copy of the LTR and the internal domain sequence. Interestingly, among the families, there are widely differing copy numbers of complete elements and LTRs: 32 Ty1 elements and 217 Ty1-type d elements; 13 Ty2 elements and 34 Ty2type d elements; two Ty3 elements and 41 s elements; 3 Ty4 elements and 32 t elements; and one Ty5 element and seven v elements. Thus, ratios of LTR sequences to complete elements range from 7 for Ty1 to 21 for Ty3. Because there are many more Ty1 insertions than Ty3 insertions and because the Ty1-type d elements are more degenerate than the s elements, Ty1 probably represents an older class of elements within yeast. The fact that the ratio of LTR to complete copies is so much higher for Ty3 suggests that generation of isolated LTRs occurs more frequently for some sequences than for others. With stunning completeness, the genome sequence reveals the nonrandom nature of the retroelement insertions for each family (see Fig. 1) (Chalker and Sandmeyer 1992; Devine and Boeke 1996; Zou et al. 1996; Bryk et al. 1997; Smith and Boeke 1997). In addition to tRNA genes, 5S, U6, and PI RNA genes were also found associated with insertions. The Tyl, Ty2, Ty3, and Ty4 elements target the upstream region of RNA polymerase 111-transcribed genes: 196 of 217 Ty1; 28 of 34 Ty2; 40 of 41 Ty3; and 30 of 32 Ty4 insertions are within 750 bp of a gene transcribed by RNA polymerase III. This listing is conservative because it does not exclude the possibility that some of the seemingly exceptional insertions are associated with unidentified targets, such as unknown or degenerate polymerase IIItranscribed genes. Ty5 does not target tRNA genes. Instead, Ty5 inserts into silenced regions of the genome, the telomeres and mating type loci. In addition to these important insights, the analysis of Kim et al. (1998) raises provocative questions concerning the relationship between repetitive elements and their habitats: Why is Saccharomyces apparently lacking major classes of elements, including quite ancient ones found in bacteria; what is the impact of these elements on genome maintenance; and why do these elements target particular genomic regions? These questions are addressed in the remainder of this article.