A role for host-parasite interactions in the horizontal transfer of transposons across phyla.

Horizontal transfer (HT), or the passage of genetic material between non-mating species, is increasingly recognized as an important force in the evolution of eukaryotic genomes. Transposons, with their inherent ability to mobilize and amplify within genomes, may be especially prone to HT. However, the means by which transposons can spread across widely diverged species remain elusive. Here we present evidence that host-parasite interactions have promoted the HT of four transposon families between invertebrates and vertebrates. We found that Rhodnius prolixus, a triatomine bug feeding on the blood of various tetrapods and vector of Chagas' disease in humans, carries in its genome four distinct transposon families that also invaded the genomes of a diverse, but overlapping, set of tetrapods. The bug transposons are approximately 98% identical and cluster phylogenetically with those of the opossum and squirrel monkey, two of its preferred mammalian hosts in South America. We also identified one of these transposon families in the pond snail Lymnaea stagnalis, a cosmopolitan vector of trematodes infecting diverse vertebrates, whose ancestral sequence is nearly identical and clusters with those found in Old World mammals. Together these data provide evidence for a previously hypothesized role of host-parasite interactions in facilitating HT among animals. Furthermore, the large amount of DNA generated by the amplification of the horizontally transferred transposons supports the idea that the exchange of genetic material between hosts and parasites influences their genomic evolution.

Horizontal SPINning of transposons.

The term 'horizontal transfer (HT)' refers to the transfer of genetic material between two reproductively isolated organisms. HT is thought to occur rarely in eukaryotes compared to vertical inheritance, the transmission of DNA from parent to offspring. In a recent study we have provided evidence that a family of DNA transposons, called SPACE INVADERS or SPIN, independently invaded horizontally the genome of seven distantly related tetrapod species and subsequently amplified to high copy number in each of them. This discovery calls for further investigations to better characterize the extent to which genomes have been shaped through HT events. In this addendum, we briefly discuss some general issues regarding the study of HT and further speculate on the sequence of events that could explain the current taxonomic distribution of SPIN. We propose that the presence of SPIN in the opossum (Monodelphis domestica), a taxon endemic to South America, reflects a transoceanic HT event that occurred from Old to New World, between 46 and 15 million years ago.

Repair-mediated duplication by capture of proximal chromosomal DNA has shaped vertebrate genome evolution.

DNA double-strand breaks (DSBs) are a common form of cellular damage that can lead to cell death if not repaired promptly. Experimental systems have shown that DSB repair in eukaryotic cells is often imperfect and may result in the insertion of extra chromosomal DNA or the duplication of existing DNA at the breakpoint. These events are thought to be a source of genomic instability and human diseases, but it is unclear whether they have contributed significantly to genome evolution. Here we developed an innovative computational pipeline that takes advantage of the repetitive structure of genomes to detect repair-mediated duplication events (RDs) that occurred in the germline and created insertions of at least 50 bp of genomic DNA. Using this pipeline we identified over 1,000 probable RDs in the human genome. Of these, 824 were intra-chromosomal, closely linked duplications of up to 619 bp bearing the hallmarks of the synthesis-dependent strand-annealing repair pathway. This mechanism has duplicated hundreds of sequences predicted to be functional in the human genome, including exons, UTRs, intron splice sites and transcription factor binding sites. Dating of the duplication events using comparative genomics and experimental validation revealed that the mechanism has operated continuously but with decreasing intensity throughout primate evolution. The mechanism has produced species-specific duplications in all primate species surveyed and is contributing to genomic variation among humans. Finally, we show that RDs have also occurred, albeit at a lower frequency, in non-primate mammals and other vertebrates, indicating that this mechanism has been an important force shaping vertebrate genome evolution.

Repeated horizontal transfer of a DNA transposon in mammals and other tetrapods.

Horizontal transfer (HT) is central to the evolution of prokaryotic species. Selfish and mobile genetic elements, such as phages, plasmids, and transposons, are the primary vehicles for HT among prokaryotes. In multicellular eukaryotes, the prevalence and evolutionary significance of HT remain unclear. Here, we identified a set of DNA transposon families dubbed SPACE INVADERS (or SPIN) whose consensus sequences are approximately 96% identical over their entire length (2.9 kb) in the genomes of murine rodents (rat/mouse), bushbaby (prosimian primate), little brown bat (laurasiatherian), tenrec (afrotherian), opossum (marsupial), and two non-mammalian tetrapods (anole lizard and African clawed frog). In contrast, SPIN elements were undetectable in other species represented in the sequence databases, including 19 other mammals with draft whole-genome assemblies. This patchy distribution, coupled with the extreme level of SPIN identity in widely divergent tetrapods and the overall lack of selective constraint acting on these elements, is incompatible with vertical inheritance, but strongly indicative of multiple horizontal introductions. We show that these germline infiltrations likely occurred around the same evolutionary time (15-46 mya) and spawned some of the largest bursts of DNA transposon activity ever recorded in any species lineage (nearly 100,000 SPIN copies per haploid genome in tenrec). The process also led to the emergence of a new gene in the murine lineage derived from a SPIN transposase. In summary, HT of DNA transposons has contributed significantly to shaping and diversifying the genomes of multiple mammalian and tetrapod species.

Target site analysis of RTE1_LA and its AfroSINE partner in the elephant genome.

SINEs retrotranspose using their partner LINE's enzymatic machinery. It has recently been proposed that AfroSINEs ending with GGTTT 3' tandem repeats were mobilized by RTE elements ending with CAA 3' tandem repeats in the Afrotherian genome. Using sequences from the elephant genome, we show that AfroSINEs derive from RTE ending with GGTTT-like 3' tandem repeats, a subgroup of RTE1_LA that only reached low copy number, and confirm that they were most likely mobilized by RTE ending with CAA(n) tandem repeats (RTE1_LA-CAA(n)). This partnership is supported by sequence similarity between two regions of the elements, overlap in the timing of their activity, common features of their target site consensus that are not shared by other members of the RTE family, and their high copy number. Detailed analyses of pre-insertion loci reveal that like many other apurinic/apyrimidinic endonuclease encoding elements, RTE1_LA-CAA(n) shows loose target site specificity. In addition, the RTE1_LA-CAA(n) target site consensus shares several structural and primary sequence features with that of LINE1, suggesting that these two elements share close functional similarity in the target primed reverse transcription (TPRT) reaction. Interestingly, although globally similar, the target site consensus of AfroSINE(Anc) and RTE1_LA-CAA(n) differ in several aspects. These differences, not observed among all SINE/LINE pairs so far examined, are most likely due to the fact that AfroSINEs and RTE1_LA-CAA(n) are terminated by a different tandem repeat motif. We propose that these differences reflect constraints imposed by base pairing interactions between the mRNA 3' terminal tandem repeats and the target DNA at the onset of TPRT. So in addition to the endonuclease nicking preference, the mRNA of these elements appears to play an important role in integration site choice through a passive, post-nicking, selective process.

The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage.

Class 2, or DNA transposons, make up approximately 3% of the human genome, yet the evolutionary history of these elements has been largely overlooked and remains poorly understood. Here we carried out the first comprehensive analysis of the activity of human DNA transposons over the course of primate evolution using three independent computational methods. First, we conducted an exhaustive search for human DNA transposons nested within L1 and Alu elements known to be primate specific. Second, we assessed the presence/absence of 794 human DNA transposons at orthologous positions in 10 mammalian species using sequence data generated by The ENCODE Project. These two approaches, which do not rely upon sequence divergence, allowed us to classify DNA transposons into three different categories: anthropoid specific (40-63 My), primate specific (64-80 My), and eutherian wide (81-150 My). Finally, we used this data to calculate the substitution rates of DNA transposons for each category and refine the age of each family based on the average percent divergence of individual copies to their consensus. Based on these combined methods, we can confidently estimate that at least 40 human DNA transposon families, representing approximately 98,000 elements ( approximately 33 Mb) in the human genome, have been active in the primate lineage. There was a cessation in the transpositional activity of DNA transposons during the later phase of the primate radiation, with no evidence of elements younger than approximately 37 My. This data points to intense activity of DNA transposons during the mammalian radiation and early primate evolution, followed, apparently, by their mass extinction in an anthropoid primate ancestor.