Rapid amplification of a retrotransposon subfamily is evolving the mouse genome

Department of Genetics, University of Pennsylvania, Philadelphia 19104, USA.
Nature Genetics (Impact Factor: 29.35). 12/1998; 20(3):288-90. DOI: 10.1038/3104
Source: PubMed


Retrotransposition affects genome structure by increasing repetition and producing insertional mutations. Dispersion of the retrotransposon L1 throughout mammalian genomes suggests that L1 activity might be an important evolutionary force. Here we report that L1 retrotransposition contributes to rapid genome evolution in the mouse, because a number of L1 sequences from the T(F) subfamily are retrotransposition competent. We show that the T(F) subfamily is large, young and expanding, containing approximately 4,800 full-length members in strain 129. Eleven randomly isolated, full-length T(F) elements averaged 99.8% sequence identity to each other, and seven of these retrotransposed in cultured cells. Thus, we estimate that the mouse genome contains approximately 3,000 active T(F) elements, 75 times the estimated number of active human L1s. Moreover, as T(F) elements are polymorphic among closely related mice, they have retrotransposed recently, implying rapid amplification of the subfamily to yield genomes with different patterns of interspersed repetition. Our data show that mice and humans differ considerably in the number of active L1s, and probably differ in the contribution of retrotransposition to ongoing sequence evolution.

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Available from: Ralph J Deberardinis, Apr 13, 2014
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    • "Among both LTR and LINE, several families showed strong enrichment in the H3K9me3 mark, while other families showed no enrichment or even depletion. Interestingly, in both classes, families that are known to be transcriptionally and tranpositionally active, such as the LTR families IAPEz, IAPEy, and MaLR (Smit 1993; Baust et al. 2003; Svoboda et al. 2004; Zhang et al. 2008) and the LINE families L1-Gf, T, and A (DeBerardinis et al. 1998; Naas et al. 1998; Mears and Hutchison 2001), had high levels of H3K9me3. A highly active but nonautonomous LTR family, ETn, was also enriched for the H3K9me3 mark, as was L1-F, which is transcribed at high levels but is thought to be incapable of transposition due to mutations in the ORF (Adey et al. 1991). "
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    ABSTRACT: Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments.
    Genes & Development 06/2014; 28(13). DOI:10.1101/gad.240895.114 · 10.80 Impact Factor
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    • "Estimated ages, counts and retrotransposition frequencies of L1 subfamily members have varied considerably. The average ages of L1 TF elements range from 0.25 to 1.23 million years old (15), and numbers of full-length insertions range from 3400 (4,68) to ∼4800 (15), whereas active and/or polymorphic TF elements ranged from ∼1900 (4) to 3000 (68). The average ages of L1 GF subfamily members have been estimated at 0.75 to 2.16 million years (15). "
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    ABSTRACT: Between 6 and 30% of human and mouse transcripts are initiated from transposable elements. However, the promoters driving such transcriptional activity are mostly unknown. We experimentally characterized an antisense (AS) promoter in mouse L1 retrotransposons for the first time, oriented antiparallel to the coding strand of L1 open reading frame-1. We found that AS transcription is mediated by RNA polymerase II. Rapid amplification of cDNA ends cloning mapped transcription start sites adjacent to the AS promoter. We identified >100 novel fusion transcripts, of which many were conserved across divergent mouse lineages, suggesting conservation of potential functions. To evaluate whether AS L1 transcription could regulate L1 retrotransposition, we replaced portions of native open reading frame-1 in donor elements by synonymously recoded sequences. The resulting L1 elements lacked AS promoter activity and retrotransposed more frequently than endogenous L1s. Overexpression of AS L1 transcripts also reduced L1 retrotransposition. This suppression of retrotransposition was largely independent of Dicer. Our experiments shed new light on how AS fusion transcripts are initiated from endogenous L1 elements across the mouse genome. Such AS transcription can contribute substantially both to natural transcriptional variation and to endogenous regulation of L1 retrotransposition.
    Nucleic Acids Research 02/2014; 42(7). DOI:10.1093/nar/gku091 · 9.11 Impact Factor
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    • "For instance families L1MdA_I, L1MdA_II, and L1MdA_III are subsets of the previously described L1MdA family; family L1MdA_I is younger than family L1MdA_II and family L1MdA_III is the oldest of the three. We kept the Gf [43] and Tf [42] names for the recently active Tf and Gf families because these names have been widely used in the literature. "
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    ABSTRACT: Background LINE-1 (L1) is the dominant category of transposable elements in placental mammals. L1 has significantly affected the size and structure of all mammalian genomes and understanding the nature of the interactions between L1 and its mammalian host remains a question of crucial importance in comparative genomics. For this reason, much attention has been dedicated to the evolution of L1. Among the most studied elements is the mouse L1 which has been the subject of a number of studies in the 1980s and 1990s. These seminal studies, performed in the pre-genomic era when only a limited number of L1 sequences were available, have significantly improved our understanding of L1 evolution. Yet, no comprehensive study on the evolution of L1 in mouse has been performed since the completion of this genome sequence. Results Using the Genome Parsing Suite we performed the first evolutionary analysis of mouse L1 over the entire length of the element. This analysis indicates that the mouse L1 has recruited novel 5’UTR sequences more frequently than previously thought and that the simultaneous activity of non-homologous promoters seems to be one of the conditions for the co-existence of multiple L1 families or lineages. In addition the exchange of genetic information between L1 families is not limited to the 5’UTR as evidence of inter-family recombination was observed in ORF1, ORF2, and the 3’UTR. In contrast to the human L1, there was little evidence of rapid amino-acid replacement in the coiled-coil of ORF1, although this region is structurally unstable. We propose that the structural instability of the coiled-coil domain might be adaptive and that structural changes in this region are selectively equivalent to the rapid evolution at the amino-acid level reported in the human lineage. Conclusions The pattern of evolution of L1 in mouse shows some similarity with human suggesting that the nature of the interactions between L1 and its host might be similar in these two species. Yet, some notable differences, particularly in the evolution of ORF1, suggest that the molecular mechanisms involved in host-L1 interactions might be different in these two species.
    Mobile DNA 01/2013; 4(1):3. DOI:10.1186/1759-8753-4-3 · 2.11 Impact Factor
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