Although bacterial genomes have been traditionally viewed as being very compact, with relatively low amounts of repetitive and non-coding DNA, this view has dramatically changed in recent years. The increase of available complete bacterial genomes has revealed that many species present abundant repetitive DNA (i.e., insertion sequences, prophages or paralogous genes) and that many of these sequences are not functional but can have evolutionary consequences as concerns the adaptation to specialized host-related ecological niches. Comparative genomics analyses with close relatives that live in non-specialized environments reveal the nature and fate of this bacterial junk DNA. In addition, the number of insertion sequences and pseudogenes, as well as the size of the intergenic regions, can be used as markers of the evolutionary stage of a genome. Full article

There is a mounting body of evidence that somatic transposition may be involved in normal development of multicellular organisms and in pathology, especially cancer. Epigenetic Tracking (ET) is an abstract model of multicellular development, able to generate complex 3-dimensional structures. Its aim is not to model the development of a particular organism nor to merely summarise mainstream knowledge on genetic regulation of development. Rather, the goal of ET is to provide a theoretical framework to test new postulated genetic mechanisms, not fully established yet in mainstream biology. The first proposal is that development is orchestrated through a subset of cells which we call driver cells. In these cells, the cellular state determines a specific pattern of gene activation which leads to the occurrence of developmental events. The second proposal is that evolution of development is affected by somatic transposition events. We postulate that when the genome of a driver cell does not specify what developmental event should be undertaken when the cell is in a particular cellular state, somatic transposition events can reshape the genome, build new regulatory regions, and lead to a new pattern of gene activation in the cell. Our third hypothesis, not supported yet by direct evidence, but consistent with some experimental observations, is that these new “no-junk” sequences—regulatory regions created by transposable elements at new positions in the genome—can exit the cell and enter the germline, to be incorporated in the genome of the progeny. We call this mechanism germline penetration. This process allows heritable incorporation of novel developmental events in the developmental trajectory. In this paper we will present the model and link these three postulated mechanisms to biological observations. Full article

After finishing a human genome reference sequence in 2002, the genomics community has turned to the task of interpreting it. A primary focus is to identify and characterize not only protein-coding genes, but all functional elements in the genome. The effort includes both individual investigators and large-scale projects like the Encyclopedia of DNA Elements (ENCODE) project. As part of the ENCODE project, several groups have identified millions of regulatory elements in hundreds of human cell-types using DNase-seq and FAIRE-seq experiments that detect regions of nucleosome-free open chromatin. ChIP-seq experiments have also been used to discover transcription factor binding sites and map histone modifications. Nearly all identified elements are found in non-coding DNA, hypothesizing a function for previously unannotated sequence. In this review, we provide an overview of the ENCODE effort to define regulatory elements, summarize the main results, and discuss implications of the millions of regulatory elements distributed throughout the genome. Full article

Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms (SNPs) have been the major focus of most large-scale comparative genomics studies to date. Here, we discuss a third, largely ignored, type of genetic variation, namely changes in tandem repeat number. Historically, tandem repeats have been designated as non functional “junk” DNA, mostly as a result of their highly unstable nature. With the exception of tandem repeats involved in human neurodegenerative diseases, repeat variation was often believed to be neutral with no phenotypic consequences. Recent studies, however, have shown that as many as 10% to 20% of coding and regulatory sequences in eukaryotes contain an unstable repeat tract. Contrary to initial suggestions, tandem repeat variation can have useful phenotypic consequences. Examples include rapid variation in microbial cell surface, tuning of internal molecular clocks in flies and the dynamic morphological plasticity in mammals. As such, tandem repeats can be useful functional elements that facilitate evolvability and rapid adaptation. Full article

Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions in Ewing sarcoma are a prime example of this, resulting in potent chimeric oncoproteins with novel biological properties and a unique transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, the most common EWS/ETS fusion in Ewing sarcoma, upregulates gene expression using a GGAA microsatellite response element dispersed throughout the human genome. These GGAA microsatellites function as enhancer elements, are sites of epigenetic regulation and are necessary for EWS/FLI DNA binding and upregulation of principal oncogenic targets. An increasing number of GGAA motifs appear to substantially enhance EWS/FLI-mediated gene expression, which has compelling biological implications as these GGAA microsatellites are highly polymorphic within and between ethnically distinct populations. Historically regarded as junk DNA, this emerging evidence clearly demonstrates that microsatellite DNA plays an instrumental role in EWS/FLI-mediated transcriptional regulation and oncogenesis in Ewing sarcoma. This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand our mechanistic understanding of how EWS/ETS fusions influence cancer susceptibility, prognosis and transcriptional regulation. Full article

One of the most unexpected insights that followed from the completion of the human genome a decade ago was that more than half of our DNA is derived from transposable elements (TEs). Due to advances in high throughput sequencing technologies it is now clear that TEs comprise the largest molecular class within most metazoan genomes. TEs, once categorised as "junk DNA", are now known to influence genomic structure and function by increasing the coding and non-coding genetic repertoire of the host. In this way TEs are key elements that stimulate the evolution of metazoan genomes. This review highlights several lines of TE research including the horizontal transfer of TEs through host-parasite interactions, the vertical maintenance of TEs over long periods of evolutionary time, and the direct role that TEs have played in generating morphological novelty. Full article

Despite recent technological advances, the study of the human transcriptome is still in its early stages. Here we provide an overview of the complex human transcriptomic landscape, present the bioinformatics challenges posed by the vast quantities of transcriptomic data, and discuss some of the studies that have tried to determine how much of the human genome is transcribed. Recent evidence has suggested that more than 90% of the human genome is transcribed into RNA. However, this view has been strongly contested by groups of scientists who argued that many of the observed transcripts are simply the result of transcriptional noise. In this review, we conclude that the full extent of transcription remains an open question that will not be fully addressed until we decipher the complete range and biological diversity of the transcribed genomic sequences. Full article

The past decade has seen dramatic changes in our understanding of the scale and complexity of eukaryotic transcriptome owing to the discovery of diverse types of short and long non-protein-coding RNAs (ncRNAs). While short ncRNA-mediated gene regulation has been extensively studied and the mechanisms well understood, the function of long ncRNAs remains largely unexplored, especially in plants. Nevertheless, functional insights generated in recent studies with mammalian systems have indicated that long ncRNAs are key regulators of a variety of biological processes. They have been shown to act as transcriptional regulators and competing endogenous RNAs (ceRNAs), to serve as molecular cargos for protein re-localization and as modular scaffolds to recruit the assembly of multiple protein complexes for chromatin modifications. Some of these functions have been found to be conserved in plants. Here, we review our current understanding of long ncRNA functions in plants and discuss the challenges in functional characterization of plant long ncRNAs. Full article

During interphase, chromosomes are relatively de-condensed in the nuclear space. Interphase chromosomes are known to occupy nuclear space in a non-random manner (chromosome territory); however, their internal structures are poorly defined. In particular, little is understood about the molecular mechanisms that govern the internal organization of interphase chromosomes. The author recently proposed that pairing (or interaction) of repetitive DNA-containing chromatin regions is a critical driving force that specifies the higher-order organization of eukaryotic chromosomes. Guided by this theoretical framework and published experimental data on the structure of interphase chromosomes and the spatial distribution of repetitive DNA in interphase nuclei, I postulate here a molecular structure of chromatin organization in interphase chromosomes. According to this model, an interphase chromosome is a chromatin mesh (or lattice) that is formed by repeat pairing (RP). The mesh consists of two types of structural components: chromosome nodes and loose chromatin fibers. Chromosome nodes are DNA repeat assemblies (RAs) that are formed via RP, while loose fibers include chromatin loops that radiate from the nodes. Different loops crosslink by RPs and form a large integrated chromatin network. I suggest that the organization of the chromatin network of a given interphase chromosome is intrinsically specified by the distribution of repetitive DNA elements on the linear chromatin. The stability of the organization is governed by the collection of RA-formed nodes, and the dynamics of the organization is driven by the assembling and disassembling of the nodes. Full article