生命誕生の過程では，多種多様な生命構成単位（building blocks of life; BBLs）を合成するための強力な外部エネルギーが必要である．太陽エネルギーは化学進化を駆動するには弱すぎるうえ，夜間のエネルギー供給はゼロである．それゆえ他のエネルギー源が必要である．その有力な候補の一つが，冥王代地球表層に普遍的に存在していたと考えられる自然原子炉である．自然原子炉起源のウランの崩壊熱と電離放射線は前駆的化学進化において重要な役割を担う．電離放射線のように，十分な活性化エネルギーがコンスタントに確保されと，無機分子からより複雑な有機分子が合成されうる．こうした反応は，太陽光やマグマ由来の熱では到底不可能である．つまり，生命誕生へ向けた最初のプロセスは電離放射線が駆動したと考えられる．自然原子炉と間欠泉が組み合わさり物質・エネルギー循環系が形成されると，初期生命の誕生に向けたさまざまな反応が試行され，代謝と自己複製の機能がつくられたと推定される．間欠泉によって大気中に放出されたミクロンサイズの液滴飛沫が，もっとも原始的な細胞をつくりだし，より複雑化した膜やさまざまなBBLsの組み合わせをつくりだしたのであろう．さらに地上に放出された多種多様な原始細胞は，強力かつ豊富なエネルギー源である自然原子炉から離れたことが原因で，生き残りをかけて，やがて太陽光を利用する新たな機能を獲得したのであろう．表紙の画像は，生命進化を駆動する重要なエネルギー源である自然原始炉と太陽を対照的に描いたもので，地球と生命の誕生，共進化，未来を描いた12編からなるCG動画集「全地球史アトラス」¹⁾の１シーンである．

（丸山茂徳）

Notes

1) YouTube; https://www.youtube.com/c/冥王代生命学の創成 (in Japanese) or https://www.youtube.com/c/HadeanBioscience (in English) [Cited 2020/10/27].

 Reported are the origins and chemistry of hot spring water unique to the Ohmi–Hakuba region in the northern Japan Alps, central north Honshu, where a variety of rock types, derived from accretionary complex formed in the Ediacaran (presumably ca. 620 Ma), are regionally exposed. One of the largest bodies of serpentinized peridotite in Japan intersects the Quaternary volcanic front. Featuring an unusual geochemistry, the resulting unique hydrothermal hot springs yield a high pH (ca. 10-11) and a continuous supply of H₂. Research reveals four types of hot spring in the Hakuba region: (1) serpentinite hosted hot spring water, (2) high-salinity and carbonated water, (3) Archean type low pO₂ hot spring water, and (4) acidic and sulfuric hot spring water with a H₂S gas input from magma. The high alkali and H₂-enriched hot spring water (Type 1) differs remarkably from other hot springs in this region. In terms of geochemistry, there is a dissolved oxygen content due to the production of abundant H₂, which is the reason why a Hadean-type microbial community is present. The origins and evolution of life are closely related to atmospheric oxygen level. Generally, anaerobic microbes inhabit subsurface areas where free oxygen is limited, while oxygen adaptive creatures cannot survive in an anaerobic environment. This means anaerobic microbes have not evolved, and remain as “living fossils”. Hakuba OD1 is one of the most important candidates for the oldest form of life directly connected to LUCA, because it has survived in a Hadean-like environment since emerging. The next research target is the ecosystem in a H₂-enriched environment without free oxygen.

 Previously proposed hypotheses on the origin of life are reviewed and it is demonstrated that none of them can provide the energy flux of ionizing radiation (UV/X/γ photons, and high-energy charged particles and neutrons) required to synthesize organic materials as demonstrated by the experiments by Miller and Urey in 1953. In order to overcome this difficulty, Ebisuzaki and Maruyama, in 2017, proposed a new hypothesis called the “Nuclear Geyser Model” of the origin of life, in which high-energy flux from a natural nuclear reactor drives chemical reactions to produce major biological molecules, such as amino acids, nucleotides, sugars, and fatty acids from raw molecules (H₂O, N₂, and CO₂). Natural nuclear reactors were common on the surface of Hadean Earth, because the ²³⁵U/²³⁸U ratio was as high as 20%, which is much higher than the present value (0.7%), due to the shorter half-life of ²³⁵U than ²³⁸U. Ebisuzaki and Maruyama further posited that aqueous electrons and glyceraldehyde play key roles in the networks of chemical reactions in a nuclear geyser and suggested that primordial life depended on glyceraldehyde phosphate (GAP) from the nuclear geyser system as energy, carbon, and phosphate sources, pointing to a possible parallelism with the anaerobic glycolysis pathway; in particular, the lower stem path starting from GAP through Acetyl Coenzyme A to produce ATP and reduction power. It is shown that microbes (members of candidate division OD1) inhabiting high alkali hot springs, a modern analogue of the Hadean Earth environment, do not possess genes associated with conventional metabolisms, such as those of the TCA cycle, but only have genes in the lower stem path of the glycolysis. This is named the “Hadean Primordial Pathway”, because it is believed that this striking result points to a plausible origin of metabolic pathways of extant organisms. Also proposed is a step-by-step scenario of the evolution of the metabolism: 1) Chemical degradation of GAP supplied from the nuclear geyser to lactate; 2) Catalytic reactions to produce reductive power and acetyl coenzyme A (or its primitive form) and self-reproductive reactions by ribozymes on the surface of minerals (pyrite and struvite), which precipitate in a nuclear geyser (RNA world); 3) Enzymatic reactions by proteins with pyrites and the struvite in their reaction centers (RNP world); and, 4) Metabolism of extant organisms with the full assembly of enzymes produced by translating molecular machines with information stored in DNA sequences (DNA world). It is further inferred that relics of primordial metabolic evolution in the Hadean nuclear geyser can be seen at the reaction centers of enzymes of both pyrite and struvite types, nucleotide-like molecules as a cofactor of the enzymes, Calvin Cycle of photosynthesis, and chemical abundance of cytoplasm.

 Estimating the “minimal gene set” for a cell to be viable is an important issue in understanding “living” cells, creating “artificial” cells, and revealing “ancient” cells. The minimal gene set is critical information for understanding a cell system and designing an artificial genome, which is an essential element for creating an artificial cell. Artificial cells can provide many clues to understanding primordial life on Earth. To reveal minimal gene sets, “essential genes” in many bacteria, which could not be removed from bacterial genomes, have been identified. Bacteria are the most useful organisms for identifying essential genes from their specific characteristics: small genomes, rapid growth, and species that are easy to manipulate genetically. Therefore, various investigations on minimal gene sets or minimal genome of bacteria are reviewed, and “the minimal gene set for a viable cell” is discussed.

 To date, more than 15,000 bacterial and archaeal species have been isolated and characterized. It has become evident from recent biochemical and genomic studies that these microorganisms employ a variety of energy conservation systems to drive thermodynamically unfavorable reactions or harness marginal energy from exergonic reactions in the metabolic pathways required for energy metabolism. For example, a membrane-bound [NiFe] hydrogenase (Mbh) supports critical steps in glycolysis for a hyper-thermophilic archaeon Pyrococcus furiosus: glyceraldehyde 3-phosphate (GAP):ferredoxin (Fd) oxidoreductase and pyruvate:Fd oxidoreductase. However, the molecular evolution of energy conservation systems is still poorly understood. Targets of this study are: [NiFe] hydrogenase-related energy conservation systems including Mbh, energy conserving hydrogenases (Eha, Ehb, and Ech), hydrogenase 3 (Hyc), hydrogenase 4 (Hyf), hydrogen-evolving NADH/quinone-dependent hydrogenases (Hya and Hyb), and bidirectional soluble hydrogenase (Hox). A phylogenetic analysis shows that subunits having a [NiFe] active site of mbh (mbhL), which catalyzes proton reduction, are closely related to subunits of other energy conserving hydrogenases (i.e., ehaO, ehbN, and echE), and are distantly related to other subunits of [NiFe] hydrogenases (i.e., hya and hox) and NADH:ubiquinone oxidoreductase subunit D (nuoD). Combined phylogenetic analysis of hydrogenase-associated proton pomp modules indicates that ancestral Mbh containing mbhL and mbhH may have served as an energy conservation system for primordial metabolism.

 Chemical evolution, starting from simple compounds that eventually transform into complex mixtures, is a theme long recognized to be of fundamental importance to origins of life research. Ionizing radiation on simple and small molecules, such as hydrogen cyanide (HCN) and acetonitorile (CH₃CN), is proposed to be one of the geochemically plausible mechanism driving multiple reactions yielding prebiotic precursors essential to emergence of life on early-Earth. Water radiolysis forming radicals, proton, and solvated electron also assists developing a reaction network in a one-pot system. Radiolytic mechanisms on an experimental basis are reviewed. Particularly, proposed synthetic strategies and mechanisms of amino acids and nucleotides are presented.

 The origin of life has been explained by a number of hypotheses. Depending on the geochemical settings in each hypothesis, model metabolisms of the first life are classified into two major types, namely, heterotrophy and autotrophy. The “Iron-sulfur world” hypothesis explains the development of autotrophic life with a chemical evolution process mediated by metal sulfides. Metal sulfides have been found to catalyze simple carbon/nitrogen reduction reactions in simulated Hadean Earth conditions. Combinations of these reactions are thought to form organic molecules, such as pyruvate and peptide, then ultimately the first cell. Iron-sulfur proteins are found in all life and play a cardinal role in key redox/oxidation reactions, such as carbon/nitrogen fixation, respiration, and translation. Ancient iron-sulfur proteins are hypothesized to be formed by the conjugation of iron-sulfur clusters and simple peptides. First, an overview is given of the “Iron-sulfur world” hypothesis including the chemical evolution process for the formation of ancient iron-sulfur proteins, and then future perspectives for the origin-of-life research are discussed in the context of this hypothesis.

 All living organisms found so far consist of cells with a micro-water droplet surrounded by a lipid bilayer. Such a compartment structure is necessary for living organisms to repress the amplification of parasitic entities. This role of cellular structures is especially important for the primitive lifeforms that first appeared on ancient Earth. This complex lipid-based cell boundary is considered to have been acquired later in the long evolutionary history of life. Instead, ancient life-forms utilized cell-like structures that could be supplied from the ancient Earth environment. What kinds of structure could be utilized by ancient life-forms? Reviewed here are previous hypotheses regarding ancient cell-like structures, such as compartment structures formed inside a hydrothermal vent or on a rock surface, water droplets in the air that spread from geysers, and vesicles composed of simple amphiphilic molecules. Also introduced are a recent experimental verification of droplets in the air repressing parasite amplification using Spiegelman's RNA replication system. Our understanding of the origins of cellular structures is still limited because of a lack of appropriate experimental examinations based on a deeper understanding of the ancient Earth environment, which can be achieved only by collaborations between geologists and biochemists.

 It is well known that the evolution of life is affected by environmental factors, and this should be a fundamental perspective when investigating the origin of life; however, this perspective has not been fully addressed in biology. The Hadean Earth had a completely different surface environment from that of today, with no free oxygen, but instead a local environment rich in H₂ which was generated by serpentinization, while energy–material circulation was driven by nuclear geysers. It is proposed that an anoxic hot-spring environment, with abundant hydrogen produced by serpentinization, was the birthplace of life. It is also proposed that the Hakuba hot spring in Nagano, Japan, is a Hadean-Earth-like environment with an H₂-rich environment. A microbe found there, designated Hakuba OD1, is a member of the Candidate Phyla Radiation (CPR) bacteria group. In this review, CPR bacteria are described and their importance for the origin of life is discussed. The CPR is a bacterial supergroup consisting of dozens of phylum-level lineages of very small bacteria. This group was recently discovered with a metagenomics analysis that allowed unculturable environmental samples to be detected. Biochemical approaches to the CPR bacteria have not yet been successful because almost all the bacteria are unculturable or have not been isolated. However, with the development of massive parallel sequencing technology (next-generation sequencing), the phylogenetic characteristics of the CPR bacteria are becoming clear, and genomic analyses of these bacteria have led to unique discoveries. The sizes of the CPR bacterial genomes range from 400 to 1,500 kilobases (kb), and they contain approximately 400-1,500 genes. Thus, their genomes are remarkably small compared to other well-known and ordinary bacteria, represented by Escherichia coli, which have over 4,000 genes, but are similar to those of symbiotic or parasitic bacteria. The CPR bacterial genomes also lack many of the genes involved in essential metabolic pathways, such as the tricarboxylic acid (TCA) cycle and amino acid biosynthesis, so they seem to obtain their essential metabolites from their environments. It is proposed that this knowledge is important when considering the chemical changes that occurred on primitive Earth, which gave rise to the first forms of life through the processes of chemical evolution. Therefore, it is essential to understand the kinds of protein that are encoded in CPR bacterial genomes when studying the origin of life.

 The origin of eukaryotic organisms is one of the most important questions in biology. So far, it has been suggested that eukaryotes are phylogenetically related to Archaea. Indeed, recent progress in archaeal genomic biology seems to have accurately determined the exact position of Archaea in the birth of the Eukaryota. In particular, identifying groups of archaeal species, such as the superphylum TACK and the Asgard archaea, has shown that primitive genes for eukaryotic signature proteins (ESP) already existed in the genomes of these archaeal species. Some ESPs are especially important, including actin and tubulin in the cytoskeleton and the ESCRT complex, which is involved in nuclear membrane formation. There have been many reports that eukaryotic intracellular organelles, such as mitochondria and chloroplasts, evolved from specific symbiotic bacteria. Moreover, eukaryotic genes are disrupted by intronic sequences, which must be removed or “spliced” and the exons connected after the primary transcript is generated, to make a mature functional mRNA. Recently, it has been suggested that the self-splicing factor in both bacterial and archaeal genomes, called “group II intron”, may cause gene disruption. In this review, the frontiers of genome biology are summarized in terms of the importance of prokaryotes (both Archaea and Bacteria) for the origin of Eukarya. From an Earth history perspective, how the increase in atmospheric oxygen concentration at 2.4-2.0 billion years ago may have contributed to the rise of the eukaryotes is discussed.