The impact of transposable elements on eukaryotic genomes: From genome size increase to genetic adaptation to stressful environments

Transposable elements (TEs) are present in roughly all genomes. These mobile DNA sequences are able to invade genomes and their impact on genome evolution is substantial. The mobility of TEs can induce the appearance of deleterious mutations, gene disruption and chromosome rearrangements, but transposition activity also has positive aspects and the mutational activities of TEs contribute to the genetic diversity of organisms. This short review aims to give a brief overview of the impact TEs may have on animal and plant genome structure and expression, and the relationship between TEs and the stress response of organisms, including insecticide resistance.     

Classification and nomenclature of endogenous retroviral sequences (ERVs): Problems and recommendations

The genomes of many species are crowded with repetitive mobile sequences. In the case of endogenous retroviruses (ERVs) there is, for various reasons, considerable confusion regarding names assigned to families/groups of ERVs as well as individual ERV loci. Human ERVs have been studied in greater detail, and naming of HERVs in the scientific literature is somewhat confusing not just to the outsider. Without guidelines, confusion for ERVs in other species will also probably increase if those ERVs are studied in greater detail. Based on previous experience, this review highlights some of the problems when naming and classifying ERVs, and provides some guidance for detecting and characterizing ERV sequences. Because of the close relationship between ERVs and exogenous retroviruses (XRVs) it is reasonable to reconcile their classification with that of XRVs. We here argue that classification should be based on a combination of similarity, structural features, (inferred) function, and previous nomenclature. Because the RepBase system is widely employed in genome annotation, RepBase designations should be considered in further taxonomic efforts. To lay a foundation for a phylogenetically based taxonomy, further analyses of ERVs in many hosts are needed. A dedicated, permanent, international consortium would best be suited to integrate and communicate our current and future knowledge on repetitive, mobile elements in general to the scientific community.     

Expression profiles of human endogenous retrovirus (HERV)-K and HERV-R Env proteins in various cancers

The vertebrate genome contains an endogenous retrovirus that has been inherited from the past millions of years. Although approximately 8% of human chromosomal DNA consists of sequences derived from human endogenous retrovirus (HERV) fragments, most of the HERVs are currently inactive and non-infectious due to recombination, deletions, and mutations after insertion into the host genome. Several studies suggested that Human endogenous retroviruses (HERVs) factors are significantly related to certain cancers. However, only limited studies have been conducted to analyze the expression of HERV derived elements at protein levels in certain cancers. Herein, we analyzed the expression profiles of HERV-K envelope (Env) and HERV-R Env proteins in eleven different kinds of cancer tissues. Furthermore, the expression patterns of both protein and correlation with various clinical data in each tissue were analyzed. The expressions of both HERV-K Env and HERV-R Env protein were identified to be significantly high in most of the tumors compared with normal surrounding tissues. Correlations between HERV Env expressions and clinical investigations varied depending on the HERV types and cancers. Overall expression patterns of HERV-K Env and HERV-R Env proteins were different in every individual but a similar pattern of expressions was observed in the same individual. These results demonstrate the expression profiles of HERV-K and HERV-R Env proteins in various cancer tissues and provide a good reference for the association of endogenous retroviral Env proteins in the progression of various cancers. Furthermore, the results elucidate the relationship between HERV-Env expression and the clinical significance of certain cancers.     

Loss of epigenetic silencing in tumors preferentially affects primate-specific retroelements

Close to 50% of the human genome harbors repetitive sequences originally derived from mobile DNA elements, and in normal cells, this sequence compartment is tightly regulated by epigenetic silencing mechanisms involving chromatin-mediated repression. In cancer cells, repetitive DNA elements suffer abnormal demethylation, with potential loss of silencing. We used a genome-wide microarray approach to measure DNA methylation changes in cancers of the head and neck and to compare these changes to alterations found in adjacent non-tumor tissues. We observed specific alterations at thousands of small clusters of CpG dinucleotides associated with DNA repeats. Among the 257,599 repetitive elements probed, 5% to 8% showed disease-related DNA methylation alterations. In dysplasia, a large number of local events of loss of methylation appear in apparently stochastic fashion. Loss of DNA methylation is most pronounced for certain members of the SVA, HERV, LINE-1P, AluY, and MaLR families. The methylation levels of retrotransposons are discretely stratified, with younger elements being highly methylated in healthy tissues, while in tumors, these young elements suffer the most dramatic loss of methylation. Wilcoxon test statistics reveals that a subset of primate LINE-1 elements is demethylated preferentially in tumors, as compared to non-tumoral adjacent tissue. Sequence analysis of these strongly demethylated elements reveals genomic loci harboring full length, as opposed to truncated elements, while possible enrichment for functional LINE-1 ORFs is weaker. Our analysis suggests that, in non-tumor adjacent tissues, there is generalized and highly variable disruption of epigenetic control across the repetitive DNA compartment, while in tumor cells, a specific subset of LINE-1 retrotransposons that arose during primate evolution suffers the most dramatic DNA methylation alterations.     

用巢式RT-PCR检测精神分裂症患者血液标本中HERV env基因

精神分裂症是一种复杂的大脑功能紊乱疾病,表现为认知、情绪、感官的失调,有研究认为遗传因素及环境因素对大脑发育成熟过程的影响与精神分裂症的发生有关[1]。最近报道发现,人内源性逆转录病毒的转录激活可能与某些精神分裂症患者的发病有关[2]。HERV的激活可能影响邻近基因的转录调控,或者以其编码的病毒蛋白,影响细胞的代谢,从而导致疾病的发生[3]。本实验采用巢式RT-PCR方法检测急性精神分裂症患者和正常人PBMCs中HERV-W env(包膜基因)的表达,探讨HERV的转录激活与精神分裂症发生的关系。1材料与方法28例急性精神分裂症患者血…     

Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates

HERV-FRD is a human endogenous retrovirus that entered the human genome 40 million years ago. Its envelope gene, syncytin-2, was diverted by an ancestral host most probably because of its fusogenic property, for a role in placenta morphogenesis. It was maintained in a functional state in all primate branches as a bona fide cellular gene, submitted to a very low mutation rate as compared to infectious retrovirus genomes. The structure of the syncytin-2 protein thus provides a good insight into that of the oldest mammalian retroviral envelope. Here, we report the crystal structure of a central fragment of its "fossil" ectodomain, allowing a remarkable superposition with the structures of the corresponding domains of present-day infectious retroviruses, in spite of a more than 60% divergent sequence. These results suggest the existence of a unique structural solution selected by these proteins for their fusogenic function.     

内源性逆转录病毒长末端重复序列在嗜酸性粒细胞增多症的基因表达及核苷酸序列分析

探索人内源性逆转录病毒长末端重复序列(LTR)基因及表达与嗜酸性粒细胞增多症发生的关系。PCR法检测嗜酸性粒细胞增多症患者外周血中内源性逆转录病毒长末端重复序列基因,RT-PCR法检测内源性逆转录病毒基因表达。变性高效液相分析和序列测定LTR片段核苷酸序列,对不同株基因序列作同源性的比较分析。PCR结果显示:20例嗜酸性粒细胞增多症患者细胞中均获得内源性逆转录病毒长末端重复序列扩增产物,嗜酸性粒细胞增多症组中长末端重复序列基因有高的表达,而正常人表达为阴性。与HERV-K家族LTR基因相应区域核苷酸序列比较;嗜酸性粒细胞增多组长末端重复序列U3、R、U5区同源性分析有核苷酸的改变,与淋巴瘤对照比较没有大片段的缺失。人类基因组中普遍存在逆转录病毒长末端重复序列。正常人和嗜酸性粒细胞增多症患者中长末端重复序列有不同程度核苷酸碱基的变异,但是,二者比较,这种改变与嗜酸性粒细胞的增多没有明显的相关性。在嗜酸性粒细胞增多症患者中有高的基因表达而正常人中没有可检出的病毒基因的表达,嗜酸粒细胞的增多可能与逆转录病毒基因表达水平有关,其诱导嗜酸粒细胞增多的机制需进一步的研究。     

Transcriptome Analyses Implicate Endogenous Retroviruses Involved in the Host Antiviral Immune System through the Interferon Pathway

Virologica Sinica - Human endogenous retroviruses (HERVs) are the remains of ancient retroviruses that invaded our ancestors’ germline cell and were integrated into the genome. The expression...