Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor samples from 133 cases, we have delineated the entire landscape of somatic alterations, and discovered frequently affected driver pathways in PTCL, NOS, with and without a T-follicular helper (TFH) cell phenotype. In addition to previously reported mutational targets, we identified a number of novel recurrently altered genes, such as KMT2C, SETD1B, YTHDF2, and PDCD1. We integrated these genetic drivers using hierarchical clustering and identified a previously undescribed molecular subtype characterized by TP53 and/or CDKN2A mutations and deletions in non-TFH PTCL, NOS. This subtype exhibited different prognosis and unique genetic features associated with extensive chromosomal instability, which preferentially affected molecules involved in immune escape and transcriptional regulation, such as HLA-A/B and IKZF2. Taken together, our findings provide novel insights into the molecular pathogenesis of PTCL, NOS by highlighting their genetic heterogeneity. These results should help to devise a novel molecular classification of PTCLs and to exploit a new therapeutic strategy for this group of aggressive malignancies.

Transcriptomics has the potential to discover new RNA virus genomes by sequencing total intracellular RNA pools. In this study, we have searched publicly available transcriptomes for sequences similar to viruses of the Nidovirales order. We report two potential nidovirus genomes, a highly divergent 35.9 kb likely complete genome from the California sea hare Aplysia californica, which we assign to a nidovirus named Aplysia abyssovirus 1 (AAbV), and a coronavirus-like 22.3 kb partial genome from the ornamented pygmy frog Microhyla fissipes, which we assign to a nidovirus named Microhyla alphaletovirus 1 (MLeV). AAbV was shown to encode a functional main proteinase, and a translational readthrough signal. Phylogenetic analysis suggested that AAbV represents a new family, proposed here as Abyssoviridae. MLeV represents a sister group to the other known coronaviruses. The importance of MLeV and AAbV for understanding nidovirus evolution, and the origin of terrestrial nidoviruses are discussed.

Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan plateau (QTP) and adjacent areas are characterized by being highly adaptive to the cold and hypoxic environment of the plateau, as well as by a high degree of diversity in trophic morphology due to resource polymorphisms. Although convergent and parallel evolution are prevalent in the organisms of the QTP, it remains unknown whether similar evolutionary patterns have occurred in the schizothoracine fishes. Here, we constructed for the first time a tentative molecular phylogeny of the schizothoracine fishes based on the complete sequences of the cytochrome b gene. We employed this molecular phylogenetic framework to examine the evolution of trophic morphologies. We used Pagel's maximum likelihood method to estimate the evolutionary associations of trophic morphologies and food resource use. Our results showed that the molecular and published morphological phylogenies of Schizothoracinae are partially incongruent with respect to some intergeneric relationships. The phylogenetic results revealed that four character states of five trophic morphologies and of food resource use evolved at least twice during the diversification of the subfamily. State transitions are the result of evolutionary patterns including either convergence or parallelism or both. Furthermore, our analyses indicate that some characters of trophic morphologies in the Schizothoracinae have undergone correlated evolution, which are somewhat correlated with different food resource uses. Collectively, our results reveal new examples of convergent and parallel evolution in the organisms of the QTP. The adaptation to different trophic niches through the modification of trophic morphologies and feeding behaviour as found in the schizothoracine fishes may account for the formation and maintenance of the high degree of diversity and radiations in fish communities endemic to QTP.

Anuran metamorphosis is an excellent system in which to study postembryonic development. Studies on Xenopus (Mesobatrachia) show that thyroid hormone receptors (TRs) regulate metamorphosis in a ligand-dependent manner by coordinating the action of hundreds of genes. However, whether this mechanism is conserved among amphibians is still unknown. To understand the molecular mechanism of this universal phenomenon, we report the transcriptional profiles of the three key developmental stages in Microhyla fissipes (Neobatrachia): premetamorphosis (PM), metamorphic climax (MC) and completion of metamorphosis (CM). In total, 2,293 differentially expressed genes were identified from comparisons of transcriptomes, and these genes showed stage-specific expression patterns. Unexpectedly, we found that TRα was highly expressed in Xenopus laevis and Bufo gargarizans at premetamorphosis but showed low expression in M. fissipes. In contrast, TRβ was highly expressed during metamorphosis in M. fissipes and X. laevis. This result may imply that TRβ is essential for initiating metamorphosis, at least in M. fissipes. Thus, our work not only identifies genes that are likely to be involved in Neobatrachia metamorphosis but also clarifies the roles of unliganded TRα in regulating tadpole growth and timing of metamorphosis, which may be conserved in anurans, and the role of liganded TRβ in launching metamorphosis.