Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. It is characterized by highly complex karyotypes with structural and numerical chromosomal alterations. The observed OS-specific characteristics in localization and frequencies of chromosomal breakages strongly implicate a specific set of responsible driver genes or a specific mechanism of fragility induction. In this study, a comprehensive assessment of somatic copy number alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently targeted by SCNAs were identified. Breakage analysis revealed OS specific unstable regions in which well-known OS tumor suppressor genes, including TP53, RB1, WWOX, DLG2 and LSAMP are located. Certain genomic features, such as transposable elements and non-B DNA-forming motifs were found to be significantly enriched in the vicinity of chromosomal breakage sites. A complex breakage pattern-chromothripsis-has been suggested as a widespread phenomenon in OS. It was further demonstrated that hyperploidy and in particular chromothripsis were strongly correlated with OS patient clinical outcome. The revealed OS-specific fragility pattern provides novel clues for understanding the biology of OS.

The domesticated silkworm (Bombyx mori) was domesticated from wild silkworm (Bombyx mandarina) more than 5,000 years ago. During domestication, body color between B. mandarina and B. mori changed dramatically. However, the molecular mechanism of the silkworm body color transition is not known. In the present study, we examined within-and between-species nucleotide diversity for eight silkworm melanin synthesis pathway genes, which play a key role in cuticular pigmentation of insects. Our results showed that the genetic diversity of B. mori was significantly lower than that of B. mandarina and 40.7% of the genetic diversity of wild silkworm was lost in domesticated silkworm. We also examined whether position effect exists among melanin synthesis pathway genes in B. mandarina and B. mori. We found that the upstream genes have significantly lower levels of genetic diversity than the downstream genes, supporting a functional constraint hypothesis (FCH) of metabolic pathway, that is, upstream enzymes are under greater selective constraint than downstream enzymes because upstream enzymes participate in biosynthesis of a number of metabolites. We also investigated whether some of the melanin synthesis pathway genes experienced selection during domestication. Neutrality test, coalescent simulation, as well as network and phylogenetic analyses showed that tyrosine hydroxylase (TH) gene was a domestication locus. Sequence analysis further suggested that a putative expression enhancer (Abd-B-binding site) in the intron of TH gene might be disrupted during domestication. TH is the rate-limiting enzyme of melanin synthesis pathway in insects. Real-time polymerase chain reaction assay did show that the relative expression levels of TH gene in B. mori were significantly lower than that in B. mandarina at three different developmental stages, which is consistent with light body color of domesticated silkworm relative to wild silkworm. Therefore, we speculated that expression change of TH gene may contribute to the body color transition from B. mandarina to B. mori. Our results emphasize the exceptional role of gene expression regulation in morphological transition of domesticated animals.

Transposable elements (TEs) are important for host gene regulation and genome evolution. Consensus sequences of TEs can assist investigators in accelerating studies on TE origins, amplification, functions and evolution, as well as comparative analyses and prediction of TEs in different species. In evolution, physiology, ecology and heredity research, fish are important models. However, to date, no comprehensive resource for TE consensus sequences exists for fish. Here, we collected genome-wide data and developed a novel database, FishTEDB, including 27 bony fishes, 1 cartilaginous fish, 1 lamprey and 1 lancelet. De novo , structure-based and homology-based approaches were combined to detect TEs. The database is open-source and user-friendly, and users can browse, search and download all data. FishTEDB also provides GetORF, BLAST and HMMER tools to analyze sequences. Database URL : http://www.fishtedb.org/

Class 2 or DNA transposons populate the genomes of most eukaryotes and like other mobile genetic elements have a profound impact on genome evolution. Most DNA transposons belong to the cut-and-paste types, which are relatively simple elements characterized by terminal-inverted repeats (TIRs) flanking a single gene encoding a transposase. All eukaryotic cut-and-paste transposons so far described are also characterized by target site duplications (TSDs) of host DNA generated upon chromosomal insertion. Here, we report a new group of evolutionarily related DNA transposons called Spy, which also include TIRs and DDE motif-containing transposase but surprisingly do not create TSDs upon insertion. Instead, Spy transposons appear to transpose precisely between 5′-AAA and TTT-3′ host nucleotides, without duplication or modification of the AAATTT target sites. Spy transposons were identified in the genomes of diverse invertebrate species based on transposase homology searches and structure-based approaches. Phylogenetic analyses indicate that Spy transposases are distantly related to IS5, ISL2EU, and PIF/Harbinger transposases. However, Spy transposons are distinct from these and other DNA transposon superfamilies by their lack of TSD and their target site preference. Our findings expand the known diversity of DNA transposons and reveal a new group of eukaryotic DDE transposases with unusual catalytic properties.

The silkworm, Bombyx mori, is one of the major insect model organisms, and its draft and fine genome sequences became available in 2004 and 2008, respectively. Transposable elements (TEs) constitute ∼40% of the silkworm genome. To better understand the roles of TEs in organization, structure and evolution of the silkworm genome, we used a combination of de novo, structure-based and homology-based approaches for identification of the silkworm TEs and identified 1308 silkworm TE families. These TE families and their classification information were organized into a comprehensive and easy-to-use web-based database, BmTEdb. Users are entitled to browse, search and download the sequences in the database. Sequence analyses such as BLAST, HMMER and EMBOSS GetORF were also provided in BmTEdb. This database will facilitate studies for the silkworm genomics, the TE functions in the silkworm and the comparative analysis of the insect TEs.Database URL: http://gene.cqu.edu.cn/BmTEdb/.