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 1, 2. Transposons, with their inherent ability to mobilize and amplify within genomes, may be especially prone to HT3 -7. 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 diverse tetrapods and vector of the 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 ~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 nearly 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 hostparasite interactions in facilitating HT among animals 3,7 . 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 influence their genomic evolution.In order to examine the factors underlying HT among widely diverged taxa we began our investigation with SPACE INVADERS (or SPIN), a recently described DNA transposon that has undergone repeated episodes of HT across the genomes of seven tetrapod lineages 5 . We first performed a series of BLASTN searches using the SPIN superconsensus sequence 5 as a query against all GenBank databases (see Methods), including 102 species for which whole genome shotgun (WGS) sequences are available. In addition to the vertebrates previously known to harbor SPIN, we found highly significant hits (e-values as low as 0, corresponding here to 86% identity over >1 kb) in the triatomine bug, Rhodnius prolixus, an hemipteran insect that feeds on the blood of mammals, birds, and reptiles and serves as a vector forCorrespondence and requests for materials should be addressed to C.F. (cedric@uta.edu). * These authors contributed equally to this work Supplementary Information is linked to the online version of the paper at www.nature.com/nature. Author Contributions C.G., S.S., and C.F. designed research, performed research, and analyzed data. J.K.P. contributed data and perl scripts. P.J.B. contributed reagents/material. C.G., S.S., and C.F. wrote the paper. Supplementary Fig. 2), a pattern indicative of the accumulation of discrete substitutions in each copy and consistent with neutral evolution of transposons after their integration in the genome...

Class 2, or DNA transposons, make up ∼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 ∼98,000 elements (∼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 ∼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.

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 Ϸ96% 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. genome evolution ͉ lateral gene transfer ͉ transposable elements ͉ transposase L ateral or horizontal transfer (HT), the transfer of genetic material between reproductively isolated species, is a frequent occurrence in prokaryotes with selfish and mobile genetic elements such as phages, plasmids, and transposons, serving as the primary vehicles for HT of prokaryotic genes (1). In contrast, reports of HT are scarce in eukaryotes and most cases of nuclear acquisition implicate transfers from prokaryotes or endosymbionts (2-6). The best documented instances of HT between the nuclear genomes of multicellular eukaryotes involve mobile genetic elements, and in particular class 2 or DNA mediated transposons (7,8). Thus far, conspicuous cases of HT of DNA transposons have been detected among insects (8-12), fish (13) and, in one example, between plants (14). Germline invasions by retroviruses have been documented for several mammals (15-18), and there is mounting evidence supporting the horizontal introduction of a snake retroposon in ruminants (19,20). However, to our knowledge, there has been no substantiated report of HT of DNA transposons in mammals. Here, we present unequivocal evidence for the repeated HT of a DNA transposon family named SPACE INVADERS in 7 tetrapod lineages, including 5 mammalian orders. ResultsDiscovery of SPIN Transposons. While surveying DNA transposons in the draft...

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.

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.

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