The evolution of retrotransposon regulatory regions and its consequences on the Drosophila melanogaster and Homo sapiens host genomes

It has now been established that transposable elements (TEs) make up a variable, but significant proportion of the genomes of all organisms, from Bacteria to Vertebrates. However, in addition to their quantitative importance, there is increasing evidence that TEs also play a functional role within the genome. In particular, TE regulatory regions can be viewed as a large pool of potential promoter sequences for host genes. Studying the evolution of regulatory region of TEs in different genomic contexts is therefore a fundamental aspect of understanding how a genome works. In this paper, we first briefly describe what is currently known about the regulation of TE copy number and activity in genomes, and then focus on TE regulatory regions and their evolution. We restrict ourselves to retrotransposons, which are the most abundant class of eukaryotic TEs, and analyze their evolution and the subsequent consequences for host genomes. Particular attention is paid to much-studied representatives of the Vertebrates and Invertebrates, Homo sapiens and Drosophila melanogaster, respectively, for which high quality sequenced genomes are available.     

The evolution of retrotransposon regulatory regions and its consequences on the Drosophila melanogaster and Homo sapiens host genomes

It has now been established that transposable elements (TEs) make up a variable, but significant proportion of the genomes of all organisms, from Bacteria to Vertebrates. However, in addition to their quantitative importance, there is increasing evidence that TEs also play a functional role within the genome. In particular, TE regulatory regions can be viewed as a large pool of potential promoter sequences for host genes. Studying the evolution of regulatory region of TEs in different genomic contexts is therefore a fundamental aspect of understanding how a genome works. In this paper, we first briefly describe what is currently known about the regulation of TE copy number and activity in genomes, and then focus on TE regulatory regions and their evolution. We restrict ourselves to retrotransposons, which are the most abundant class of eukaryotic TEs, and analyze their evolution and the subsequent consequences for host genomes. Particular attention is paid to much-studied representatives of the Vertebrates and Invertebrates, Homo sapiens and Drosophila melanogaster, respectively, for which high quality sequenced genomes are available.     

Online analysis of development

The genomics revolution has altered the very nature of research in molecular biology, from how to find genes to how to find out what specific genes do. Given the availability of so many fully (or nearly) sequenced genomes, it is now relatively easy to track down dozens or even hundreds of genes relevant to a particular field of study. Unfortunately, up till now, the tools for determining what these genes actually do in embryos and cells have not kept pace, but the burgeoning field of bioinformatics should help correct this shortcoming and introduce the power of genomics to the study of developmental biology. In this review, some of the bioinformatics resources relevant to developmental biologists are described along with some simple approaches for applying these tools to analyzing early development.     

Modular organization in the reductive evolution of protein-protein interaction networks

Background  

The variation in the sizes of the genomes of distinct life forms remains somewhat puzzling. The organization of proteins into domains and the different mechanisms that regulate gene expression are two factors that potentially increase the capacity of genomes to create more complex systems. High-throughput protein interaction data now make it possible to examine the additional complexity generated by the way that protein interactions are organized.     

From basepairs to birdsongs: phylogenetic data in the age of genomics

Given the quantity of molecular data now available, including complete genomes for some organisms, one can ask whether there is a need for any data beyond complete genomic sequences for phylogenetic analysis. One reason to look beyond the genome is that not all character information is encoded in organismal genomes. We propose a hierarchy of characters that ranges from biologically transmitted but nongenomically encoded characters, such as bird songs, to characters that are genomically encoded. All of these characters can retain historical information and are potentially useful for phylogenetic analysis. In addition, a number of phenotypic levels that are expressions of the genome can be identified. The question whether it is worth including any of these levels if all of the underlying sequence data have been collected arises, since issues of redundancy occur. Utilization of phenotypic levels that are ultimately based on sequences may facilitate reconstructing homologies that are not evident from sequence data alone. We propose the use of simultaneous analysis of sequence data and as many levels of phenotypic characters as possible to take advantage of homology information that may be more easily recovered from the latter. A method that eliminates redundancy to the degree that it can be detected is proposed.     

Genome semantics, in silico multicellular systems and the Central Dogma

Genomes with their complexity and size present what appears to be an impossible challenge. Scientists speak in terms of decades or even centuries before we will understand how genomes and their hosts the cell and the city of cells that make up the multicellular context function. We believe that there will be surprisingly quick progress made in our understanding of genomes. The key is to stop taking the Central Dogma as the only direction in which genome research can scale the semantics of genomes. Instead a top-down approach coupled with a bottom-up approach may snare the unwieldy beast and make sense of genomes. The method we propose is to take in silico biology seriously. By developing in silico models of genomes cells and multicellular systems, we position ourselves to develop a theory of meaning for artificial genomes. Then using that develop a natural semantics of genomes.     

BGD: A Database of Bat Genomes

Bats account for ~20% of mammalian species, and are the only mammals with true powered flight. For the sake of their specialized phenotypic traits, many researches have been devoted to examine the evolution of bats. Until now, some whole genome sequences of bats have been assembled and annotated, however, a uniform resource for the annotated bat genomes is still unavailable. To make the extensive data associated with the bat genomes accessible to the general biological communities, we established a Bat Genome Database (BGD). BGD is an open-access, web-available portal that integrates available data of bat genomes and genes. It hosts data from six bat species, including two megabats and four microbats. Users can query the gene annotations using efficient searching engine, and it offers browsable tracks of bat genomes. Furthermore, an easy-to-use phylogenetic analysis tool was also provided to facilitate online phylogeny study of genes. To the best of our knowledge, BGD is the first database of bat genomes. It will extend our understanding of the bat evolution and be advantageous to the bat sequences analysis. BGD is freely available at: http://donglab.ecnu.edu.cn/databases/BatGenome/.     

Dbmodeling

Genome sequencing efforts are providing us with complete genetic blueprints for hundreds of organisms. We are now faced with assigning, understanding, and modifying the functions of proteins encoded by these genomes. DBMODELING is a relational database of annotated comparative protein structure models and their metabolic pathway characterization, when identified. This procedure was applied to complete genomes such as Mycobacterium tuberculosis and Xylella fastidiosa. The main interest in the study of metabolic pathways is that some of these pathways are not present in humans, which makes them selective targets for drug design, decreasing the impact of drugs in humans. In the database, there are currently 1116 proteins from two genomes. It can be accessed by any researcher at http://www. biocristalografia.df.ibilce. unesp.br/tools/. This project confirms that homology modeling is a useful tool in structural bioinformatics and that it can be very valuable in annotating genome sequence information, contributing to structural and functional genomics, and analyzing protein-ligand docking.     

A genomic view of 500 million years of cnidarian evolution

Cnidarians (corals, anemones, jellyfish and hydras) are a diverse group of animals of interest to evolutionary biologists, ecologists and developmental biologists. With the publication of the genome sequences of Hydra and Nematostella, whose last common ancestor was the stem cnidarian, researchers are beginning to see the genomic underpinnings of cnidarian biology. Cnidarians are known for the remarkable plasticity of their morphology and life cycles. This plasticity is reflected in the Hydra and Nematostella genomes, which differ to an exceptional degree in size, base composition, transposable element content and gene conservation. It is now known what cnidarian genomes, given 500 million years, are capable of; as we discuss here, the next challenge is to understand how this genomic history has led to the striking diversity seen in this group.     

A brief history of the status of transposable elements: from junk DNA to major players in evolution

The idea that some genetic factors are able to move around chromosomes emerged more than 60 years ago when Barbara McClintock first suggested that such elements existed and had a major role in controlling gene expression and that they also have had a major influence in reshaping genomes in evolution. It was many years, however, before the accumulation of data and theories showed that this latter revolutionary idea was correct although, understandably, it fell far short of our present view of the significant influence of what are now known as "transposable elements" in evolution. In this article, I summarize the main events that influenced my thinking about transposable elements as a young scientist and the influence and role of these specific genomic elements in evolution over subsequent years. Today, we recognize that the findings about genomic changes affected by transposable elements have considerably altered our view of the ways in which genomes evolve and work.     

BAC libraries and comparative genomics of aquatic chordate species

The bacterial artificial chromosome (BAC) system is useful for creating a representation of the genomes of target species. The system is advantageous in that it can accommodate exogenous inserts that are very large (>100 kilobases, kb), thereby allowing entire eukaryotic genes (including flanking regulatory regions) to be encompassed in a single clone. The interest in BACs has recently been spawned by vast improvements in high throughput genomic sequencing such that comparisons of orthologous regions from different genomes (comparative genomics) are being routinely investigated, and comprise a significant component, of all major sequencing centers. In this review, we discuss the general principles of BAC cloning, the resources that are currently available, and some of the applications of the technology. It is not intended to be an exhaustive treatise; rather our goal is to provide a primer of the BAC technology in order to make readers aware of these resources and how they may utilize them in their own research programs.     

Modern mRNA proofreading and repair: clues that the last universal common ancestor possessed an RNA genome?

RNA repair has now been demonstrated to be a genuine biological process and appears to be present in all three domains of life. In this article, we consider what this might mean for the transition from an early RNA-dominated world to modern cells possessing genetically encoded proteins and DNA. There are significant gaps in our understanding of how the modern protein-DNA world could have evolved from a simpler system, and it is currently uncertain whether DNA genomes evolved once or twice. Against this backdrop, the discovery of RNA repair in modern cells is timely food for thought and brings us conceptually one step closer to understanding how RNA genomes were replaced by DNA genomes. We have examined the available literature on multisubunit RNA polymerase structure and function and conclude that a strong case can be made that the Last Universal Common Ancestor (LUCA) possessed a repair-competent RNA polymerase, which would have been capable of acting on an RNA genome. However, while this lends credibility to the proposal that the LUCA had an RNA genome, the alternative, that LUCA had a DNA genome, cannot be completely ruled out.     

An update on chloroplast genomes

Plant cells possess two more genomes besides the central nuclear genome: the mitochondrial genome and the chloroplast genome (or plastome). Compared to the gigantic nuclear genome, these organelle genomes are tiny and are present in high copy number. These genomes are less prone to recombination and, therefore, retain signatures of their age to a much better extent than their nuclear counterparts. Thus, they are valuable phylogenetic tools, giving useful information about the relative age and relatedness of the organisms possessing them. Unlike animal cells, mitochondrial genomes of plant cells are characterized by large size, extensive intramolecular recombination and low nucleotide substitution rates and are of limited phylogenetic utility. Chloroplast genomes, on the other hand, show resemblance to animal mitochondrial genomes in terms of phylogenetic utility and are more relevant and useful in case of plants. Conservation in gene order, content and lack of recombination make the plastome an attractive tool for plant phylogenetic studies. Their importance is reflected in the rapid increase in the availability of complete chloroplast genomes in the public databases. This review aims to summarize the progress in chloroplast genome research since its inception and tries to encompass all related aspects. Starting with a brief historical account, it gives a detailed account of the current status of chloroplast genome sequencing and touches upon RNA editing, ycfs, molecular phylogeny, DNA barcoding as well as gene transfer to the nucleus.     

A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering

The last 50 years of molecular genetics have produced an abundance of new discoveries and data that make it useful to revisit some basic concepts and assumptions in our thinking about genomes and evolution. Chief among these observations are the complex modularity of genome organization, the biological ubiquity of mobile and repetitive DNA sequences, and the fundamental importance of DNA rearrangements in the evolution of sequenced genomes. This review will take a broad overview of these developments and suggest some new ways of thinking about genomes as sophisticated informatic storage systems and about evolution as a systems engineering process.     

Laying the foundation for a Genomic Rosetta Stone: creating information hubs through the use of consensus identifiers

Given the growing wealth of downstream information, the integration of molecular and non-molecular data on a given organism has become a major challenge. For micro-organisms, this information now includes a growing collection of sequenced genes and complete genomes, and for communities of organisms it includes metagenomes. Integration of the data is facilitated by the existence of authoritative, community-recognized, consensus identifiers that may form the heart of so-called information knuckles. The Genomic Standards Consortium (GSC) is building a mapping of identifiers across a group of federated databases with the aim to improve navigation across these resources and to enable the integration of their information in the near future. In particular, this is possible because of the existence of INSDC Genome Project Identifiers (GPIDs) and accession numbers, and the ability of the community to define new consensus identifiers such as the culture identifiers used in the StrainInfo.net bioportal. Here we outline (1) the general design of the Genomic Rosetta Stone project, (2) introduce example linkages between key databases (that cover information about genomes, 16S rRNA gene sequences, and microbial biological resource centers), and (3) make an open call for participation in this project providing a vision for its future use.     

The turbulent life of Sirevirus retrotransposons and the evolution of the maize genome: more than ten thousand elements tell the story

Sireviruses are one of the three genera of Copia long terminal repeat (LTR) retrotransposons, exclusive to and highly abundant in plants, and with a unique, among retrotransposons, genome structure. Yet, perhaps due to the few references to the Sirevirus origin of some families, compounded by the difficulty in correctly assigning retrotransposon families into genera, Sireviruses have hardly featured in recent research. As a result, analysis at this key level of classification and details of their colonization and impact on plant genomes are currently lacking. Recently, however, it became possible to accurately assign elements from diverse families to this genus in one step, based on highly conserved sequence motifs. Hence, Sirevirus dynamics in the relatively obese maize genome can now be comprehensively studied. Overall, we identified >10 600 intact and approximately 28 000 degenerate Sirevirus elements from a plethora of families, some brought into the genus for the first time. Sireviruses make up approximately 90% of the Copia population and it is the only genus that has successfully infiltrated the genome, possibly by experiencing intense amplification during the last 600 000 years, while being constantly recycled by host mechanisms. They accumulate in chromosome-distal gene-rich areas, where they insert in between gene islands, mainly in preferred zones within their own genomes. Sirevirus LTRs are heavily methylated, while there is evidence for a palindromic consensus target sequence. This work brings Sireviruses in the spotlight, elucidating their lifestyle and history, and suggesting their crucial role in the current genomic make-up of maize, and possibly other plant hosts.