Yuichiro Hara

Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms.

MOTIVATION: Along with the increasing accessibility to comprehensive sequence information, such as whole genomes and transcriptomes, the demand for assessing their quality has been multiplied. To this end, metrics based on sequence lengths, such as N50, have become a standard, but they only evaluate one aspect of assembly quality. Conversely, analyzing the coverage of pre-selected reference protein-coding genes provides essential content-based quality assessment, but the currently available pipelines for this purpose, CEGMA and BUSCO, do not have a user-friendly interface to serve as a uniform environment for assembly completeness assessment. RESULTS: Here, we introduce a brand-new web server, gVolante, which provides an online tool for (i) on-demand completeness assessment of sequence sets by means of the previously developed pipelines CEGMA and BUSCO and (ii) browsing pre-computed completeness scores for publicly available data in its database section. Completeness assessments performed on gVolante report scores based on not just the coverage of reference genes but also on sequence lengths (e.g. N50 scaffold length), allowing quality control in multiple aspects. Using gVolante, one can compare the quality of original assemblies between their multiple versions (obtained through program choice and parameter tweaking, for example) and evaluate them in comparison to the scores of public resources found in the database section. AVAILABILITY AND IMPLEMENTATION: gVoalte is freely available at https://gvolante.riken.jp/. CONTACT: shigehiro.kuraku@riken.jp.

Abstract Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer’s disease (AD). Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, App NL - G - F/NL - G - F with amyloid pathology, rTg4510 with tauopathy, and SOD1 G93A with motor neuron disease by magnetic activated cell sorting. In parallel, gene expression patterns of the human precuneus with early Alzheimer’s change (n = 11) and control brain (n = 14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1 G93A microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic microglial genes was correlated with the degree of neuronal cell loss. In human precuneus with early AD pathology, reduced expression of genes related to microglia- and oligodendrocyte-specific markers was observed, although the expression of DAM genes was not upregulated. Our results implicate a loss of homeostatic microglial function in the progression of AD and other neurodegenerative diseases. Moreover, analyses of human precuneus also suggest loss of microglia and oligodendrocyte functions induced by early amyloid pathology in human.

Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.