Ginger DNA transposons in eukaryotes and their evolutionary relationships with long terminal repeat retrotransposons

Abstract

Background: In eukaryotes, long terminal repeat (LTR) retrotransposons such as Copia, BEL and Gypsy integrate their DNA copies into the host genome using a particular type of DDE transposase called integrase (INT). The Gypsy INT-like transposase is also conserved in the Polinton/Maverick self-synthesizing DNA transposons and in the 'cut and paste' DNA transposons known as TDD-4 and TDD-5. Moreover, it is known that INT is similar to bacterial transposases that belong to the IS3, IS481, IS30 and IS630 families. It has been suggested that LTR retrotransposons evolved from a non-LTR retrotransposon fused with a DNA transposon in early eukaryotes. In this paper we analyze a diverse superfamily of eukaryotic cut and paste DNA transposons coding for INT-like transposase and discuss their evolutionary relationship to LTR retrotransposons.

Results: A new diverse eukaryotic superfamily of DNA transposons, named Ginger (for 'Gypsy INteGrasE Related') DNA transposons is defined and analyzed. Analogously to the IS3 and IS481 bacterial transposons, the Ginger termini resemble those of the Gypsy LTR retrotransposons. Currently, Ginger transposons can be divided into two distinct groups named Ginger1 and Ginger2/Tdd. Elements from the Ginger1 group are characterized by approximately 40 to 270 base pair (bp) terminal inverted repeats (TIRs), and are flanked by CCGG-specific or CCGT-specific target site duplication (TSD) sequences. The Ginger1-encoded transposases contain an approximate 400 amino acid N-terminal portion sharing high amino acid identity to the entire Gypsy-encoded integrases, including the YPYY motif, zinc finger, DDE domain, and, importantly, the GPY/F motif, a hallmark of Gypsy and endogenous retrovirus (ERV) integrases. Ginger1 transposases also contain additional C-terminal domains: ovarian tumor (OTU)-like protease domain or Ulp1 protease domain. In vertebrate genomes, at least two host genes, which were previously thought to be derived from the Gypsy integrases, apparently have evolved from the Ginger1 transposase genes. We also introduce a second Ginger group, designated Ginger2/Tdd, which includes the previously reported DNA transposon TDD-4.

Conclusions: The Ginger superfamily represents eukaryotic DNA transposons closely related to LTR retrotransposons. Ginger elements provide new insights into the evolution of transposable elements and certain transposable element (TE)-derived genes.

Figure 1

Ginger1 (for 'Gypsy INteGrasE Related 1') elements and transposases. (a) Schematic features of the Ginger1 DNA transposons. Target site duplications (TSDs) and target sequences preferences of the Ginger1 and Ginger2 groups are compared, which is based on the data of 112 Ginger1 elements from Hydra magnipapillata and 64 Ginger2 elements from Nematostella vectensis. (b-d) Alignment of Ginger1 and Gypsy integrases in the YPYY motif and the H2C2 zinc finger domain (b), the DDE core domain (c), and the GPY/F motif (d). (e) Alignment of the Ulp1 and plant homeodomain (PHD) domains in Ginger1 TPases, Mutator TPases and yeast protein 1EUV_A; the PHD domain is boxed. (f) Alignment of the ovarian tumor (OTU) domains of Ginger TPases, Helitron proteins, and yeast protein 3BY4_A.

Figure 2

Phylogenetic relationship between the integrases of Ginger1 (for 'Gypsy INteGrasE Related 1'), Ginger2 and Gypsy LTR retrotransposons. The tree, based on the multiple alignments in the zinc finger domain and the DDE domain (see Additional file 1), is constructed by the minimum evolution (ME) method (Poisson correction model, pairwise deletion, gamma parameter = 2, bootstrap replicates = 1,000). The neighbor-joining (NJ) tree is shown in Additional file 2. The ME and NJ bootstrap values of major clades are shown in parenthesis, respectively. Lines in non-black colors differentiate the non-Gypsy integrases. The names of known Gypsy lineages follow previous literatures [18,20,43,44]. The eukaryotic IS481-like integrases in Trichomonas vaginalis are designated as IS418EU. The two distinct Copia clades [45] are named Copia-I and Copia-II, respectively. Integrases containing the YPYY motif are marked with red dots. The clades containing the GPY/F motif are marked with green dots.

Figure 3

Host genes evolved from Ginger1 (for 'Gypsy INteGrasE Related 1') DNA transposon. (a) The phylogenetic relationship between Gin-1, Gin-2, and the Ginger1 elements (in red). The tree is constructed by the minimum evolution (ME) method (Poisson correction model, pairwise deletion, gamma parameter = 2, 1,000 bootstrap replicates). The sequences and alignment are shown in Additional file 3. C. intestinalis_1 gene refers to XM_002130131.1 gene; C. intestinalis_2 gene corresponds to expression sequence tag (EST) named FF869668.1. Integrases from Gypsy 412/Mdg1 lineage are included as outgroups. (b) The alignment of the local sequences around the three conserved introns in Ginger1-5_HM TPase and host proteins. The arrows point to the intron positions, the Arabic numbers (above) indicate the intron phase.