Insight into the symbiotic lifestyle of DPANN archaea revealed by cultivation and genome analyses

Decades of culture-independent analyses have resulted in proposals of many tentative archaeal phyla with no cultivable representative. Members of DPANN (an acronym of the names of the first included phyla Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota, and Nanoarchaeota), an archaeal superphylum composed of at least 10 of these tentative phyla, are generally considered obligate symbionts dependent on other microorganisms. While many draft/complete genome sequences of DPANN archaea are available and their biological functions have been considerably predicted, only a few examples of their successful laboratory cultivation have been reported, limiting our knowledge of their symbiotic lifestyles. Here, we investigated physiology, morphology, and host specificity of an archaeon of the phylum “Candidatus Micrarchaeota” (ARM-1) belonging to the DPANN superphylum by cultivation. We constructed a stable coculture system composed of ARM-1 and its original host Metallosphaera sp. AS-7 belonging to the order Sulfolobales. Further host-switching experiments confirmed that ARM-1 grew on five different archaeal species from three genera—Metallosphaera, Acidianus, and Saccharolobus—originating from geologically distinct hot, acidic environments. The results suggested the existence of DPANN archaea that can grow by relying on a range of hosts. Genomic analyses showed inferred metabolic capabilities, common/unique genetic contents of ARM-1 among cultivated micrarchaeal representatives, and the possibility of horizontal gene transfer between ARM-1 and members of the order Sulfolobales. Our report sheds light on the symbiotic lifestyles of DPANN archaea and will contribute to the elucidation of their biological/ecological functions.

Misinterpretation of Genomic Data Matters for Endangered Species Listing: The Sub-specific Status of the Peñasco Least Chipmunk (Neotamias minimus atristriatus)

We provide a response to a recently published evaluation of the subspecies status of the Peñasco least chipmunk (Neotamias minimus atristriatus). The work we discuss used exon capture genomic approaches and concluded that their results did not support the distinction of this taxon as a subspecies, with recommendation that it be synonymized with N. m. operarius. We refute the interpretations, conclusions, and taxonomic recommendations of this study, and explain in clearer terms how to interpret genomic analyses for applied management. We identify four broad conceptual issues that led to errant recommendations: (1) interpretation of subspecies and diagnosability, (2) inappropriate use of reciprocal monophyly as a criterion for subspecies, (3) importance of geographic isolation, and (4) error in hypothesis testing and misinterpretation of results. We conclude that the data from this genomic appraisal add to information from prior studies providing strong support for recognition of N. m. atristriatus as a subspecies. Our conclusions have important and immediate implications for the proposed listing of N. m. atristriatus as an endangered species under the U.S. Endangered Species Act.

Acquisition of the arginine deiminase system benefits epiparasitic Saccharibacteria and their host bacteria in a mammalian niche environment

Saccharibacteria are a group of widespread and genetically diverse ultrasmall bacteria with highly reduced genomes that belong to the Candidate Phyla Radiation. Comparative genomic analyses suggest convergent evolution of key functions enabling the adaptation of environmental Saccharibacteria to mammalian microbiomes. Currently, our understanding of this environment-to-mammal niche transition within Saccharibacteria and their obligate episymbiotic association with host bacteria is limited. Here, we identified a complete arginine deiminase system (ADS), found in further genome streamlined mammal-associated Saccharibacteria but missing in their environmental counterparts, suggesting acquisition during environment-to-mammal niche transition. Using TM7x, the first cultured Saccharibacteria strain from the human oral microbiome and its host bacterium Actinomyces odontolyticus, we experimentally tested the function and impact of the ADS. We demonstrated that by catabolizing arginine and generating adenosine triphosphate, the ADS allows metabolically restrained TM7x to maintain higher viability and infectivity when disassociated from the host bacterium. Furthermore, the ADS protects TM7x and its host bacterium from acid stress, a condition frequently encountered within the human oral cavity due to bacterial metabolism of dietary carbohydrates. Intriguingly, with a restricted host range, TM7x forms obligate associations with Actinomyces spp. lacking the ADS but not those carrying the ADS, suggesting the acquired ADS may also contribute to partner selection for cooperative episymbiosis within a mammalian microbiome. These data present experimental characterization of a mutualistic interaction between TM7x and their host bacteria, and illustrate the benefits of acquiring a novel pathway in the transition of Saccharibacteria to mammalian microbiomes.

Draft Genome of Cochliopodium minus (Amoebozoa): Insights into Its Complex Sexual Behavior, Across Domain Gene Acquisitions and Metazoan Type Signaling

To date, genomic analyses in amoebozoans have been mostly limited to model organisms or medically important lineages. Consequently, the vast diversity of Amoebozoa genomes remain unexplored. A draft genome of Cochliopodium minus, an amoeba characterized by extensive cellular and nuclear fusions, is presented. C. minus has been a subject of recent investigation for its unusual sexual behavior. Cochliopodium’s sexual activity occurs during vegetative stage making it an ideal model for studying sexual development, which is sorely lacking in the group. Here we generate a C. minus draft genome assembly. From this genome, we detect a substantial number of lateral gene transfer (LGT) instances from bacteria (15%), archaea (0.9%) and viruses (0.7%) the majority of which are detected in our transcriptome data. We identify the complete meiosis toolkit genes in the C. minus genome, as well as the absence of several key genes involved in plasmogamy and karyogamy. Comparative genomics of amoebozoans reveals variation in sexual mechanism exist in the group. Similar to complex eukaryotes, C. minus (some amoebae) possesses Tyrosine kinases and duplicate copies of SPO11. We report a first example of alternative splicing in a key meiosis gene and draw important insights on molecular mechanism of sex in C. minus using genomic and transcriptomic data.

Genomic analyses identify significant processes in BCL11B-deficient aorta

BCL11B is a transcription factor, which contains profound effects on the aorta, contractile properties of resistance vessels, and blood pressure. However, the mechanism of how BCL11B regulates the aorta function is not fully understood. In this study, our study is to identify the key molecules and signaling pathways by analyzing the RNA-seq data. The GSE163551 was produced by the Illumina NextSeq 500 (Mus musculus). The KEGG and GO analyses showed the ribosome and calcium signaling pathways are the main processes during the BCL11B knockout. Moreover, we determined ten key molecules including RPS11, GATA4, RPS13, RPL9, RPL27A, RPS24, RPL23A, RPL37A, BMP4, RPS7. Thus, our study may provide novel knowledge of the BCL11B regulated aorta.

Genomic analyses identify biological processes of miR-125 mediated breast cancer cells

miRNAs contain suppressive and oncogenic properties to regulate the progression of cancers. The expression of miR-125b expression is reported to be consistently low in breast cancers. However, the function and mechanism of miR-125b are not fully understood in breast cancers. In our study, our objective is to identify the DEGs and biological processes in the miR-125b mediated breast cancer cells by analyzing the RNA-seq data. The GSE123358 dataset was produced by the Illumina HiSeq 2000 (Homo sapiens). The KEGG and GO analyses showed the mitochondria and endoplasmic reticulum oxidative phosphorylation pathways are the main processes in miR-125b mediated breast cancer. Moreover, we identified ten interactive molecules including UQCRQ, CALR, HNRNPU, ATP5G1, NDUFB11, UQCRH, HSP90B1, TGOLN2, SAP18, and XPOT. Thus, our study may benefit the treatment of breast cancer by using miR-125b.

The RNA-Binding Protein Musashi1 Regulates a Network of Cell Cycle Genes in Group 4 Medulloblastoma

Medulloblastoma is the most common malignant brain tumor in children. Treatment with surgery, irradiation, and chemotherapy has improved survival in recent years, but patients are frequently left with devastating neurocognitive and other sequelae. Patients in molecular subgroups 3 and 4 still experience a high mortality rate. To identify new pathways contributing to medulloblastoma development and create new routes for therapy, we have been studying oncogenic RNA-binding proteins. We defined Musashi1 (Msi1) as one of the main drivers of medulloblastoma development. The high expression of Msi1 is prevalent in Group 4 and correlates with poor prognosis while its knockdown disrupted cancer-relevant phenotypes. Genomic analyses (RNA-seq and RIP-seq) indicated that cell cycle and division are the main biological categories regulated by Msi1 in Group 4 medulloblastoma. The most prominent Msi1 targets include CDK2, CDK6, CCND1, CDKN2A, and CCNA1. The inhibition of Msi1 with luteolin affected the growth of CHLA-01 and CHLA-01R Group 4 medulloblastoma cells and a synergistic effect was observed when luteolin and the mitosis inhibitor, vincristine, were combined. These findings indicate that a combined therapeutic strategy (Msi1 + cell cycle/division inhibitors) could work as an alternative to treat Group 4 medulloblastoma.