The diversity of Class II transposable elements in mammalian genomes has arisen from ancestral phylogenetic splits during ancient waves of proliferation through the genome

DNA transposons make up three percent of the human genome, roughly the same percentage as genes. However, due to their inactivity, they are often ignored in favour of the more abundant, active, retroelements. Despite this relative ignominy, there are a number of interesting questions to be asked of these transposon families. One particular question relates to the timing of proliferation and inactivation of elements in a family. Does an ongoing process of turnover occur, or is the process more akin to a life cycle for the family, with elements proliferating rapidly before deactivation at a later date? We answer this question by tracing back to the most recent common ancestor of each modern transposon family, using two different methods. The first method identifies the most recent common ancestor of the species in which a family of transposon fossils can still be found, which we assume will have existed soon after the true origin date of the transposon family. The second method uses molecular dating techniques to predict the age of the most recent common ancestor element from which all elements found in a modern genome are descended. Independent data from five pairs of species are used in the molecular dating analysis: Human- Chimpanzee, Human-Orangutan, Dog-Panda, Dog-Cat and Cow-Pig. Orthologous pairs of elements from host species pairs are included, and the divergence dates of these species are used to constrain the analysis. We discover that, in general, the times to element common ancestry, for a given family, are the same for the different species pairs, suggesting that there has been no order-specific process of turnover. Furthermore, for most families, the ages of the common ancestor of the host species and of that of the elements are similar, suggesting a life cycle model for the proliferation of transposons. Where these two ages differ, in families found only in Primates and Rodentia, for example, we find that the host species date is later than that of the common ancestor of the elements, implying that there may be large deletions of elements from host species, examples of which were found in their ancestors

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure

Telomere-associated endonuclease-deficient Penelope-like retroelements in diverse eukaryotes

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of National Academy of Sciences of the USA for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of the United States of America 104 (2007): 9352-9357, doi:10.1073/pnas.0702741104.The evolutionary origin of telomerases, enzymes that maintain the ends of linear chromosomes in most eukaryotes, is a subject of debate. Penelope-like elements (PLEs) are a recently described class of eukaryotic retroelements characterized by a GIY-YIG endonuclease domain and by a reverse transcriptase domain with similarity to telomerases and group II introns. Here we report that a subset of PLEs found in bdelloid rotifers, basidiomycete fungi, stramenopiles, and plants, representing four different eukaryotic kingdoms, lack the endonuclease domain and are located at telomeres. The 5' truncated ends of these elements are telomereoriented and typically capped by species-specific telomeric repeats. Most of them also carry several shorter stretches of telomeric repeats at or near their 3’ ends, which could facilitate utilization of the telomeric G-rich 3’ overhangs to prime reverse transcription. Many of these telomere-associated PLEs occupy a basal phylogenetic position close to the point of divergence from the telomerase-PLE common ancestor, and may descend from the missing link between early eukaryotic retroelements and present-day telomerases.Financial support from NIH and the U.S. National Science Foundation (MCB-0614142

The amphioxus genome and the evolution of the chordate karyotype

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approx520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution

Review of the Application of Modern Cytogenetic Methods (FISH/GISH) to the Study of Reticulation (Polyploidy/Hybridisation).

The convergence of distinct lineages upon interspecific hybridisation, including when accompanied by increases in ploidy (allopolyploidy), is a driving force in the origin of many plant species. In plant breeding too, both interspecific hybridisation and allopolyploidy are important because they facilitate introgression of alien DNA into breeding lines enabling the introduction of novel characters. Here we review how fluorescence in situ hybridisation (FISH) and genomic in situ hybridisation (GISH) have been applied to: 1) studies of interspecific hybridisation and polyploidy in nature, 2) analyses of phylogenetic relationships between species, 3) genetic mapping and 4) analysis of plant breeding materials. We also review how FISH is poised to take advantage of nextgeneration sequencing (NGS) technologies, helping the rapid characterisation of the repetitive fractions of a genome in natural populations and agricultural plants.This work was supported by NSF grant DEB-0922003