Evolution of Interferons and Interferon Receptors

Peer reviewedPublisher PD

Cell division promotes efficient retrotransposition in a stable L1 reporter cell line

Background: Long interspersed element type one (L1) actively modifies the human genome by inserting new copies of itself. This process, termed retrotransposition, requires the formation of an L1 ribonucleoprotein (RNP) complex, which must enter the nucleus before retrotransposition can proceed. Thus, the nuclear import of L1 RNP presents an opportunity for cells to regulate L1 retrotransposition post-translationally. The effect of cell division on L1 retrotransposition has been investigated by two previous studies, which observed varied degrees of inhibition in retrotransposition when primary cell strains or cancer cell lines were experimentally arrested in different stages of the cell cycle. However, seemingly divergent conclusions were reached. The role of cell division on retrotransposition remains highly debated. Findings: To monitor both L1 expression and retrotransposition quantitatively, we developed a stable dual-luciferase L1 reporter cell line, in which a bi-directional tetracycline-inducible promoter drives the expression of both a firefly luciferase-tagged L1 element and a Renilla luciferase, the latter indicative of the level of promoter induction. We observed an additional 10-fold reduction in retrotransposition in cell-cycle arrested cells even after retrotransposition had been normalized to Renilla luciferase or L1 ORF1 protein levels. In synchronized cells, cells undergoing two mitoses showed 2.6-fold higher retrotransposition than those undergoing one mitosis although L1 expression was induced for the same amount of time. Conclusions: Our data provide additional support for an important role of cell division in retrotransposition and argue that restricting the accessibility of L1 RNP to nuclear DNA could be a post-translational regulatory mechanism for retrotransposition

Retrotransposons as drivers of Mammalian brain evolution

Retrotransposons, a large and diverse class of transposable elements that are still active in humans, represent a remarkable force of genomic innovation underlying mammalian evolution. Among the features distinguishing mammals from all other vertebrates, the presence of a neocor-tex with a peculiar neuronal organization, composition and connectivity is perhaps the one that, by affecting the cognitive abilities of mammals, contributed mostly to their evolutionary success. Among mammals, hominids and especially humans display an extraordinarily expanded cortical volume, an enrichment of the repertoire of neural cell types and more elaborate patterns of neuronal connectivity. Retrotransposon-derived sequences have recently been implicated in multiple layers of gene regulation in the brain, from transcriptional and post-transcriptional control to both local and large-scale three-dimensional chromatin organization. Accordingly, an increasing variety of neurodevelopmental and neurodegenerative conditions are being recognized to be associated with retrotransposon dysregulation. We review here a large body of recent studies lending support to the idea that retrotransposon-dependent evolutionary novelties were crucial for the emergence of mammalian, primate and human peculiarities of brain morphology and function

Differential inhibition of LINE1 and LINE2 retrotransposition by vertebrate AID/APOBEC proteins

BACKGROUND: The role of AID/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established. G to A hypermutations, the hallmark of their cytidine deaminase activity, are present in several mammalian retrotransposons. However, the role of AID/APOBEC proteins in non-mammalian retroelement restriction is not completely understood. RESULTS: Here we provide the first evidence of anti-retroelement activity of a reptilian APOBEC protein. The green anole lizard A1 protein displayed potent DNA mutator activity and inhibited ex vivo retrotransposition of LINE1 and LINE2 ORF1 protein encoding elements, displaying a mechanism of action similar to that of the human A1 protein. In contrast, the human A3 proteins did not require ORF1 protein to inhibit LINE retrotransposition, suggesting a differential mechanism of anti-LINE action of A1 proteins, which emerged in amniotes, and A3 proteins, exclusive to placental mammals. In accordance, genomic analyses demonstrate differential G to A DNA editing of LINE retrotransposons in the lizard genome, which is also the first evidence for G to A DNA editing in non-mammalian genomes. CONCLUSION: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals

Differential roles of TGIF family genes in mammalian reproduction

<p>Abstract</p> <p>Background</p> <p>TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act as transcription factors repressing TGF-β signalling. Human <it>TGIFLX </it>and its orthologue, <it>Tex1 </it>in the mouse, are X-linked genes that are only expressed in the adult testis. <it>TGIF2 </it>arose from <it>TGIF1 </it>by duplication, whereas <it>TGIFLX </it>arose by retrotransposition to the X-chromosome. These genes have not been characterised in any non-eutherian mammals. We therefore studied the TGIF family in the tammar wallaby (a marsupial mammal) to investigate their roles in reproduction and how and when these genes may have evolved their functions and chromosomal locations.</p> <p>Results</p> <p>Both <it>TGIF1 </it>and <it>TGIF2 </it>were present in the tammar genome on autosomes but <it>TGIFLX </it>was absent. Tammar <it>TGIF1 </it>shared a similar expression pattern during embryogenesis, sexual differentiation and in adult tissues to that of <it>TGIF1 </it>in eutherian mammals, suggesting it has been functionally conserved. Tammar <it>TGIF2 </it>was ubiquitously expressed throughout early development as in the human and mouse, but in the adult, it was expressed only in the gonads and spleen, more like the expression pattern of human <it>TGIFLX </it>and mouse <it>Tex1</it>. Tammar <it>TGIF2 </it>mRNA was specifically detected in round and elongated spermatids. There was no mRNA detected in mature spermatozoa. TGIF2 protein was specifically located in the cytoplasm of spermatids, and in the residual body and the mid-piece of the mature sperm tail. These data suggest that tammar <it>TGIF2 </it>may participate in spermiogenesis, like <it>TGIFLX </it>does in eutherians. <it>TGIF2 </it>was detected for the first time in the ovary with mRNA produced in the granulosa and theca cells, suggesting it may also play a role in folliculogenesis.</p> <p>Conclusions</p> <p>The restricted and very similar expression of tammar <it>TGIF2 </it>to X-linked paralogues in eutherians suggests that the evolution of <it>TGIF1</it>, <it>TGIF2 </it>and <it>TGIFLX </it>in eutherians was accompanied by a change from ubiquitous to tissue-specific expression. The distribution and localization of TGIF2 in tammar adult gonads suggest that there has been an ultra-conserved function for the TGIF family in fertility and that <it>TGIF2 </it>already functioned in spermatogenesis and potentially folliculogenesis long before its retrotransposition to the X-chromosome of eutherian mammals. These results also provide further evidence that the eutherian X-chromosome has actively recruited sex and reproductive-related genes during mammalian evolution.</p

The structural, functional and evolutionary impact of transposable elements in Eukaryotes

Transposable elements (TEs) are nearly ubiquitous in eukaryotes. The increase in genomic data, as well as progress in genome annotation and molecular biology techniques, have revealed the vast number of ways mobile elements have impacted the evolution of eukaryotes. In addition to being the main cause of difference in haploid genome size, TEs have affected the overall organization of genomes by accumulating preferentially in some genomic regions, by causing structural rearrangements or by modifying the recombination rate. Although the vast majority of insertions is neutral or deleterious, TEs have been an important source of evolutionary novelties and have played a determinant role in the evolution of fundamental biological processes. TEs have been recruited in the regulation of host genes and are implicated in the evolution of regulatory networks. They have also served as a source of protein-coding sequences or even entire genes. The impact of TEs on eukaryotic evolution is only now being fully appreciated and the role they may play in a number of biological processes, such as speciation and adaptation, remains to be deciphered

The Evolution of LINE-1 in Vertebrates

The abundance and diversity of the LINE-1 (L1) retrotransposon differ greatly among vertebrates. Mammalian genomes contain hundreds of thousands L1s that have accumulated since the origin of mammals. A single group of very similar elements is active at a time in mammals, thus a single lineage of active families has evolved in this group. In contrast, non-mammalian genomes (fish, amphibians, reptiles) harbor a large diversity of concurrently transposing families, which are all represented by very small number of recently inserted copies. Why the pattern of diversity and abundance of L1 is so different among vertebrates remains unknown. To address this issue,we performed a detailed analysis of the evolutionof active L1 in14mammalsand in3non-mammalianvertebrate model species. We examined the evolution of base composition and codon bias, the general structure, and the evolution of the different domains of L1 (50UTR, ORF1, ORF2, 30UTR). L1s differ substantially in length, base composition, and structure among vertebrates. The most variation is found in the 50UTR, which is longer in amniotes, and in the ORF1, which tend to evolve faster in mammals. The highly divergent L1familiesof lizard, frog, and fish share species-specific features suggesting that they are subjected to the same functional constraints imposed by their host. The relative conservation of the 50UTR and ORF1 in non-mammalian vertebrates suggests that the repression of transposition by the host does not act in a sequence-specific manner and did not result in an arms race, as is observed in mammals

Distribution, diversity and evolution of endogenous retroviruses in perissodactyl genomes

The evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian order Perissodactyla, with a view to understanding their impact on the evolution of modern equids (family Equidae). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization and time of activity. Our results show that subsequent to their ancestral divergence from rhinos and tapirs, equids acquired four novel ERV lineages. We show that two of these proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germline colonisation by retroviruses for over 54 million years - longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs, and their impact on equine evolution

Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization

BACKGROUND: The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs) common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10), thrombotic thrombocytopenic purpura (ADAMTS13), and Ehlers-Danlos syndrome type VIIC (ADAMTS2) in humans and belted white-spotting mutation in mice (ADAMTS20). RESULTS: Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu), chordate (Ciona) and invertebrate (Drosophila and Caenorhabditis) ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. CONCLUSIONS: The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15) that may have distinct aggrecanase and angiogenesis functions