KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Cloning and characterization of the

Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven "Baltimore classes" (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. Due to the modular organization of virus genomes, these relationships defy simple representation as lines of descent but rather form complex networks. Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. Bona fide viruses evolved from this ancestor on multiple, independent occasions via the recruitment of distinct cellular proteins as capsid subunits and other structural components of virions. The single-stranded DNA (ssDNA) viruses are a polyphyletic class, with different groups evolving by recombination between rolling-circle-replicating plasmids, which contributed the replication protein, and positive-sense RNA viruses, which contributed the capsid protein. The double-stranded DNA (dsDNA) viruses are distributed among several large monophyletic groups and arose via the combination of distinct structural modules with equally diverse replication modules. Phylogenomic analyses reveal the finer structure of evolutionary connections among RNA viruses and reverse-transcribing viruses, ssDNA viruses, and large subsets of dsDNA viruses. Taken together, these analyses allow us to outline the global organization of the virus world. Here, we describe the key aspects of this organization and propose a comprehensive hierarchical taxonomy of viruses.

https://mmbr.asm.org/content/mmbr/84/2/e00061-19.full-text.pdf

Global Organization and Proposed Megataxonomy of the Virus World

H2 metabolism is proposed to be the most ancient and diverse mechanism of energy-conservation. The metalloenzymes mediating this metabolism, hydrogenases, are encoded by over 60 microbial phyla and are present in all major ecosystems. We developed a classification system and web tool, HydDB, for the structural and functional analysis of these enzymes. We show that hydrogenase function can be predicted by primary sequence alone using an expanded classification scheme (comprising 29 [NiFe], 8 [FeFe] and 1 [Fe] hydrogenase classes) that defines 11 new classes with distinct biological functions. Using this scheme, we built a web tool that rapidly and reliably classifies hydrogenase primary sequences using a combination of k-nearest neighbors’ algorithms and CDD referencing. Demonstrating its capacity, the tool reliably predicted hydrogenase content and function in 12 newly-sequenced bacteria, archaea and eukaryotes. HydDB provides the capacity to browse the amino acid sequences of 3248 annotated hydrogenase catalytic subunits and also contains a detailed repository of physiological, biochemical and structural information about the 38 hydrogenase classes defined here. The database and classifier are freely and publicly available at http://services.birc.au.dk/hyddb/

HydDB: A web tool for hydrogenase classification and analysis

In terrestrial vertebrates, bone tissue constitutes the ‘osteoimmune’ system, which functions as a locomotor organ and a mineral reservoir as well as a primary lymphoid organ where haematopoietic stem cells are maintained. Bone and mineral metabolism is maintained by the balanced action of bone cells such as osteoclasts, osteoblasts and osteocytes, yet subverted by aberrant and/or prolonged immune responses under pathological conditions. However, osteoimmune interactions are not restricted to the unidirectional effect of the immune system on bone metabolism. In recent years, we have witnessed the discovery of effects of bone cells on immune regulation, including the function of osteoprogenitor cells in haematopoietic stem cell regulation and osteoblast-mediated suppression of haematopoietic malignancies. Moreover, the dynamic reciprocal interactions between bone and malignancies in remote organs have attracted attention, extending the horizon of osteoimmunology. Here, we discuss emerging concepts in the osteoimmune dialogue in health and disease. It is well known that immune cells can have profound effects on bone cells, but this interaction is not unidirectional. In this review, Tsukasaki and Takayanagi explore the reciprocal dialogue between bone cells and immune cells during health and disease.

Osteoimmunology: evolving concepts in bone–immune interactions in health and disease

The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (∼0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood-Ljungdahl pathway, N2-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine-dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood-Ljungdahl pathway in a hydrothermal setting.

The physiology and habitat of the last universal common ancestor

All known life forms trace back to a last universal common ancestor (LUCA) that witnessed the onset of Darwinian evolution. One can ask questions about LUCA in various ways, the most common way being to look for traits that are common to all cells, like ribosomes or the genetic code. With the availability of genomes, we can, however, also ask what genes are ancient by virtue of their phylogeny rather than by virtue of being universal. That approach, undertaken recently, leads to a different view of LUCA than we have had in the past, one that fits well with the harsh geochemical setting of early Earth and resembles the biology of prokaryotes that today inhabit the Earth's crust.

/pdf/the-last-universal-common-ancestor-between-ancient-earth-5eo6yq40hn.pdf

The last universal common ancestor between ancient Earth chemistry and the onset of genetics.

Genomes record their own history. But if we want to look all the way back to life's beginnings some 4 billion years ago, the record of microbial evolution that is preserved in prokaryotic genomes is not easy to read. Microbiology has a lot in common with geology in that regard. Geologists know that plate tectonics and erosion have erased much of the geological record, with ancient rocks being truly rare. The same is true of microbes. Lateral gene transfer (LGT) and sequence divergence have erased much of the evolutionary record that was once written in genomes, and it is not obvious which genes among sequenced genomes are genuinely ancient. Which genes trace to the last universal ancestor, LUCA? The classical approach has been to look for genes that are universally distributed. Another approach is to make all trees for all genes, and sift out the trees where signals have been overwritten by LGT. What is left ought to be ancient. If we do that, what do we find?

/pdf/physiology-phylogeny-and-luca-mqdw3zqc7i.pdf

Physiology, phylogeny, and LUCA.

Weiss et al. reply — In response to our recent paper1, Gogarten and Deamer2 write in with five paragraphs. They focus on traditional views concerning the nature of the last universal common ancestor (LUCA). We find the current exchange worthwhile in that it highlights several important differences in older and newer concepts concerning both LUCA and approaches to inference of its properties. Their first paragraph, which summarizes some, but by no means all, virtues of submarine hydrothermal vents in the context of life’s origin, requires no response, although John Baross3, Mike Russell4 and Everett Shock5 can explain far better than we can how warmly the idea that life arose at hydrothermal vents was “welcomed”2. Gogarten and Deamer’s second paragraph revisits older inferences about LUCA and the progenote that are based on the three-domain tree6. However, improved phylogenetic methods and better archaeal lineage sampling now deliver a different picture of domain relationships, called the two-domain tree, in which the archaeal partner at eukaryote origin arises from within the archaea, not as the sister of the archaea7,8. We can hardly be faulted that newer methods and data obtain the twodomain tree. Why is the issue of the threedomain verus two-domain tree important? It is this. Eukaryotes are derived from a single common ancestor that had both mitochondria and a very narrow sample of bacterial carbon and energy metabolism, demonstrating facultatively anaerobic chemoorganoheterotrophy9. Inferences about LUCA that trace eukaryotic properties to the first cells (the three-domain tree) always exclude most forms of microbial physiology — for example, nitrification, mineral oxidations, the knallgas reaction, sulfate reduction, methanogenesis, and so forth5 — and can never recover traits such as anaerobic chemolithoautotrophy or the Wood–Ljungdahl pathway in LUCA for lack of such physiology in eukaryotes. Investigations of LUCA based on a threedomain approach to the problem can therefore not recover sets of genes similar to the ones we found using phylogenetic criteria that embrace the newer two-domain tree, which has been germane to our formulations of hydrothermal origins right from the beginning10. Gogarten and Deamer also lament in this paragraph that our results lead to an inference of LUCA that is not as complex as a free-living cell2, or “halfalive”, as we put it. We will return to this point in closing. Their third paragraph deals with potential caveats of our method to address LUCA’s properties. In our paper1, under the subheading “Spelling out caveats and allowing for some LGT”, we explained the issues concerning possible false positives and possible false negatives, but in greater depth and detail than Gogarten and Deamer2. We also mentioned examples1. Their comment just restates points that we made first. The fourth paragraph complains that we do not obtain the same results as earlier studies that addressed the temperature at which LUCA lived, studies that were based upon the three-domain tree. Yes, that is correct. Our results really do differ from those in previous studies. In addition, the molecular thermometer papers they cite, which estimate growth temperatures from inferred GC content in selected regions of some genes, as modelled along the branches of the three-domain tree, would need to be repeated on the basis of more current archaeal lineage sampling along the branches of the two-domain tree7,8. In their fifth paragraph, Gogarten and Deamer criticize various aspects of the theory that life arose at hydrothermal vents, in particular the idea that the naturally chemiosmotic nature of alkaline hydrothermal vents could have been important for life’s origin. The aspects of the hydrothermal vent theory that they criticize have been developed and discussed in many earlier papers by us and others3,4,9–12. In our recent genomic investigation study, we do not modify the theory, we merely find independent, genome-based evidence compatible with it. Hence, their critique applies to older papers and not ours1, the findings of which are compatible with numerous aspects of some versions of the hydrothermal vent theory (the roles of metals, acetogenesis, methanogenesis, methyl groups, clostridia, methanogens, the acetyl-CoA pathway11), including the view that gradients3 and chemiosmosis4,9–12 were important at the origin of life. Can we be faulted that genomes deliver that result? Gogarten and Deamer2 are particularly concerned that our study did not recover complete lipid biosynthesis, but we reported a number of membrane proteins within our dataset1, indicating the presence of lipids in LUCA. Not all of the membrane proteins are drawn in Fig. 3, which summarizes physiology, but they are reported in Fig. 2 and elsewhere in the paper1. Yet, not only is lipid synthesis poorly represented, the majority of amino acid and nucleotide biosyntheses are missing too. As we wrote1, lack of such essential functions among LUCA’s gene set could indicate (1) that the missing genes unspectacularly underwent transdomain lateral gene transfer (LGT) post-LUCA, and hence were filtered out by our method, (2) that missing chemical components were provided by spontaneous abiotic syntheses during early Earth history, or (3) a combination thereof. LGT between the prokaryotic domains is both normal and natural13 and all theories for the origin of cells, without exception, require abiotic syntheses; hence, we do not see any fundamental problems here. Their examples of universally present genes that are lacking from LUCA’s list are not criticisms of our findings, rather they merely underscore what we wrote, namely that genes present in all genomes “can be affected by LGTs, such that only subsets of even universally present genes will also meet the domain monophyly criterion”1. Finally, Gogarten and Deamer2 protest that our inference of LUCA contained “ribosomes, translation, genes, and a genetic code”, offering that such a level of organization goes “far beyond what most would imagine as the first form of life”2. This is a very important comment. If the first form that Gogarten and Deamer consider to be alive lacks ribosomes, translation, genes and the genetic code, how can they possibly be worried that our version of LUCA, which has genes, ribosomes, the code, translation, exergonic carbon and energy metabolism, nitrogen fixation and many basics of cofactor biosyntheses, is only half-alive? Clearly, our version of early life1 comes much closer to something that one might find in microbial culture collections (in Reply to ‘Is LUCA a thermophilic progenote?’

Reply to 'Is LUCA a thermophilic progenote?'

The advent of environmental O2 about 2.5 billion years ago forced microbes to metabolically adapt and to develop mechanisms for O2 sensing. Sensing of O2 by [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion represents an ancient mechanism that is used by FNREc (Escherichia coli), FNRBs (Bacillus subtilis), NreBSa (Staphylococcus aureus) and WhiB3Mt (Mycobacterium tuberculosis). The phylogenetic relationship of these sensors was investigated. FNREc homologues are restricted to the proteobacteria and a few representatives from other phyla. Homologues of FNRBs and NreBSa are located within the bacilli, of WhiB3 within the actinobacteria. Archaea contain no homologues. The data reveal no similarity between the FNREc , FNRBs , NreBSa and WhiB3 sensor families on the sequence and structural levels. These O2 sensor families arose independently in phyla that were already present at the time O2 appeared, their members were subsequently distributed by lateral gene transfer. The chemistry of [4Fe-4S] and [2Fe-2S] cluster formation and interconversion appears to be shared by the sensor protein families. The type of signal output is, however, family specific. The homologues of FNREc and NreBSa vary with regard to the number of Cys residues that coordinate the cluster. It is suggested that the variants derive from lateral gene transfer and gained other functions.

Madeline C. Weiss

Papers

The physiology and habitat of the last universal common ancestor

The last universal common ancestor between ancient Earth chemistry and the onset of genetics.

Physiology, phylogeny, and LUCA.

Reply to 'Is LUCA a thermophilic progenote?'

Origin and phylogenetic relationships of [4Fe–4S]‐containing O2 sensors of bacteria