Virus Evolution Theory - Beyond Darwin's Evolution Theory -	Cat: SCI Pub: 1996 #2017
	Hideomi Nakahara (中原英臣) et.al.	20x25u

Title	Virus Evolution Theory	ウイルス進化論
Index	Preface: Virus as the Leading Player of Evolution: Biotechnology and Function of Virus: Moving Genes and Bacteria: Common Viruses of Human and Animals: Deadlock of Darwinism: The Birth of Viral Evolution: Forecast from Viral Evolution: Is the Criticism of Darwinism Taboo?: Why Human Beings evolve: x:	序文: 進化の主役はウイルスだ: バイオテクノロジーとウイルスの働き: 動く遺伝子とバクテリア: ヒトと動物の共通ウイルス: 破綻したダーウィニズム: ウイルス進化論の誕生: ウイルス進化論からの予言: ダーウィニズム批判はなぜタブーか: ヒトはなぜ進化するのか: x:
Tag	; ATL; Cytokine storm; Directional change; EB virus; Episome; ERV; Escherichia coli; F-factor; Hepatitis Type-B; HIV; Horizontal gene transfer; Host specificity; HPV; Imanishi's theory; Lentivirus; Lifestyle partitioning; Ligase; Lysogenic cycle; Lytic cycle; Medical anthropology; Methylation; Neoteny; Oncovirus; Phage therapy; Plasmid; Prophage; Pseudomona K-62; Punctuated equilibrium; R-plasmid; Recognition site; Recombinant DNA; Reductionism; Restriction enzyme; Retrovirus; Selective breeding; Specia; Superspecia; Susceptibility; Temperate bacteriophage; Vector; Vertical gene transfer; Virulent phage;

Original resume

Remarks

>Top 0. Preface: This book is written in 1996, and I'm rereading this in 2020/10 in the pandemic situation of Covid-19. This book starts such expression; "Evolution is caused by infectious disease; such as giraffe's neck became longer, or human beings evolved from Cro-Magnon Men." Evolution means a change of blueprint, or DNA of a creature. Darwin's theory of evolution is composed of mutation, natural selection, and survival of the fittest. Virus infects a creature, rewriting DNA of the infected creature; such change of DNA will be an answer of evolution. Virus functions as an organelle for the evolution.

0. 序文: plasmid: プラスミド; often carry genes that benefit the survival of the organism. bacteriophage: composed of proteins that encapsulated DNA or RNA genome, This replicate within the bacterium following the injection of their genome into its cytoplasm (=material in a cell, except the nucleus). 進化は伝染病である。 設計図(DNA)は、ウイルス感染によってDNAが書き換えられ、進化につながる。 ウイルスは進化のためのオルガネラ

>Top 1. Virus as the Leading Player of Evolution: The leading player of evolution is virus: A mew evolution theory is arousing since around 1971, which focusses that virus or plasmid (organelle) has caused evolution of a creature in a way of transmitting genes between individuals beyond species; (development of genetic engineering) Darwin's Theory: composed of natural selection and survival of the fittest. the idea of survival of the fittest came from Marthus's Population Theory. natural selection came from breeding of livestock and grains. whereas, key of the recent biotechnology is genetic engineering. Virus is an organ for evolution Virus is composed of DNA/RNA, capsid, and pilus/fimbria. >Top horizontal gene transfer; between species. vertical gene transfer of genes; between offspring In 1935, Wendell M. Stanley; succeeded to crystallized tobacco mosaic virus, clarified nucleoprotein composed of about 50 million atoms. was awarded Nobel Prize in Chemistry for 1946. Virus very selectively choose its host (=host specificity); such as rabies in dog and human, Hepatitis B virus in human and chimpanzee, and cowpox in cow, cat, human; plant virus only in plants. Virus was discovered only 50 in 50 years ago, but now several hundred. >Top Prophage: is a bacteriophage integrated into the bacterial DNA chromosome; without causing disruption of the cell. Virus can infect all creatures including animal, plant, and bacteria (called bacteriophage), but not other virus itself. Bacteriophage (also phage), abundantly in the biosphere, infects and replicates within bacteria and archaea. are seen as a possible therapy against multi-drug-resistant strains of many bacteria. have lytic cycle or lysogenic cycle; lytic cycle, the viral DNA exists as a separate free floating molecule within cell, and replicates separately from the host bacterial DNA, whereas in the lysogenic cycle the viral DNA is located within the host DNA (prophage). >Top Retrovirus: once inside the host cell, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome; the host cell treats the viral DNA as part of its own genome. Retroviruses are valuable tools in molecular biology (natural nanomachine) >Top Viral Vector: Transduction: deliver genetic material into cells; both in vivo and in vitro.

1. 進化の主役はウイルス : plasmid: a genetic structure in a cell that can replicate independently organelle: special structures within a living cell pilus, -li =fimbria, -riae: 線毛 capsid: protein shell encapsulate DNA/RNA genome. rabies: 狂犬病 chickenpox: 天然痘 Hepatitis B virus: B型肝炎ウイルス prophage: a bacteriophage without causing disruption of the bacterial cell <pro=before therapy: treatment intended to relieve a disorder vector: bacteriophage or plasmid that transfers genetic material into a cell <L. vehere, =carrier plasmid: a small circular DNA strand in the cytoplasm of a bacterium. transduction: transfer of viral DNA from one cell to another using bacteriophage vector host specificity: 宿主特異性 biopharming: 生物医薬生産 transformation: 形質転換 genetic alternation, 外部からのDNA導入で遺伝的性質を変えること; cancerationも含む transduction: 形質導入, injection of foreign DNA by a bacteriophage virus into the host bacterium transfection: 遺伝子導入 ダーウィン進化論の限界: 自然淘汰と適者生存 ウイルスは遺伝子を運ぶ 1935; タバコモザイクウイルス結晶 ウイルスの特徴: 全ての生物に感染 (ウイルス以外) 宿主をひどく選り好み 細菌性ウイルス=バクテリオファージ プロファージ: 細菌のDNAの一部 遺伝子は種を超えて伝搬 レトロウイルス: RNA ウイルスが進化を起こすオルガネラ 種は一気に変わる ベクター: 遺伝子の運び屋 (=プロファージ) 伝染病の原因としてのウイルス 天然痘、狂犬病、麻疹、インフルエンザ、癌; (テキハイガン)

>Top 2. Biotechnology and function of virus: Three major science in 20C: nuclear, electronics and biotechnology (NEB) Insulin: a peptide hormone produced by β cells of the pancreatic islets; a main anabolic hormone of the body, which regulates metabolism of carbohydrates, fats and protein by absorbing of glucose from the blood into liver, fat and skeletal muscle cells. Insulin enhances glucose uptake and metabolism in the cells, reducing blood sugar level. Decrease or loss of insulin activity results in diabetes mellitus; many diabetics must inject insulin into their bodies daily; before 1980s, insulin for diabetics came from pigs and was very expensive. type-1 diabetes mellitus and type-2 diabetes mellitus. >Top Human insulin production in E. coli: human insulin protein is composed of 51 amino acids; now produced in vast quantities by biotechnology using Escherichia coli (E. coli) 1986/4: authorized in Japan to use human insulin made by biotechnology. Biotechnology: Restriction enzyme (as scissors) DNA ligase (as glue) Plasmid or Virus (as a vector) the gene that produces human insulin was added to the genes in a E. coli bacteria; once the gene was in place, the normal cellular machinery produced it. first splice the gene into a plasmid; then infected with the plasmid. then insulin producing E. coli bacteria is cultured in bulk to create insulin. The restriction enzyme are found in bacteria & archaea and proved a defence mechanism against invading viruses; by cutting foreign DNA in a process called restriction digestion; while host DNA is protected by a modification enzyme (=metyltrasferase) that modifies the DNA and blocks cleavage (=restriction modification system). >Top The discovery of restriction enzymes allows DNA to be manipulated, leading to the development of recombinant DNA technology, allowing production of proteins such as human insulin use by diabetics. Supermouse: 1) pick up the growth hormone from the pituitary gland of a rat。 2) pick up the regulatory gene (metalthionein) from the liver of a mouse 3) connect above 1) and 2) and recombine plasmid DNA 4) transform DNA of Escherichia coli, and cultivate it. 5) inject 4) into a fertilized egg of a female mouse, and give birth it. 6) 100 days after the birth, becomes a supermouse (two times) caused by 1000 times more of the growth hormone in the liver. 7) then mating of a male supermouse and a female ordinary mouse; half of the mice will be supermice. (vertical transmission) In Darwin's Theory, such horizontal and vertical transmission of genes are mostly neglected; emphasizing stochastic mutation only.

2. バイオテクノロジーとウイルスの働き: insulin: インスリン <L. Insula, =island human insulin: ヒトインスリン; porcine -; bovine - Escherichia coli (E. coli): 大腸菌 470万塩基対 diabetes mellitus: 真性糖尿病 Restriction enzyme: 制限酵素; < bacteriophageへの感染を制限 DNA ligase: リガーゼ sticky end: 付着末端 recombinant DNA: 遺伝子組み換えDNA pituitary gland: 脳下垂体 metallothionein:メタロチオネインmetal+thio (S)+nein (<protein) DNA methylation: DNAメチル化 infectious heredity: 感染遺伝 >Top phage therapy: therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. 20Cの三大科学 >Top Sticky end: cut 付着末端: Eco R1: between G and A: Restriction enzyme recognizes a specific sequence of nucleotides (Recognition site; mostly palidromic): 5'-GAATTC-3' and 3'-CTTAAG-5' >Top DNAメチル化: DNA methylation Cytosine and methylated Cytosine スーパーマウスの作り方: 1) 大型ラット雄の成長ホルモン 2) 普通のマウスの調整遺伝子 3) 1)と2)をプラスミドDNAに組み込む 4) 大腸菌の形質転換をする 5) マウス雌の受精卵の核内に注入、マウスの子宮に移植して産ませる 6) 生後100日後に約2倍のスーパーマウスとなる 7) その後、スーパーマウス雄と普通マウス雌を交配すると、半数はスーパーマウスとなる (垂直移動) ダーウィン理論は、統計的な突然変異のみ 運び屋としてのプラスミドとウイルス 溶原ファージ:

>Top 3. Moving genes and bacteria: Drug resistance: Vector as a carrier of genes; plasmid and virus are such vectors. >Top R-Plasmid (Resistance-Plasmid): a conjugative factor in bacterial cells that promotes resistance to antibiotics, metal ions, ultraviolet radiation, and bacteriophage. multidrug resistant bacteria: shigella are resistant to not only streptomycin, but also other antibiotics such as tetracycline, sulfa drug, chloramphenicol. If such resistance occurs by mutation, the probability against one drug is estimated as $10^8; and four drugs will be $10^32$ In 1952/8 in Japan, the first antibiotic resistant bacterium was discovered; and around 1958, 80% of shigella was F-Plasmid: a cell possessing F plasmid (F+, male) can form a conjugation bridge (F pilus) to a cell lacking F plasmid (F-, female) >Top Temperate bacteriophage (⇔virulent phage): whose genetic material (=prophage) becomes an intimate part of the bacterial genome, being reproduced through many cell division cycles (=lysogenic bacterium). Prophage should be the origin of bacteriophage, while virulent phage be a kind of mutant of bacteriophage. It has been considered that bacteriophage infects a bacterium, but correctly the bacteriophage is an organ of the bacterium, whose function is to transfer DNA from the host to another host; which deeply involved in evolution. Bacteriophage is an organelle to transfer genes from a bacterium to another one. a creature needs to change its genes to evolve; by mutation or by bacterial conjugation or by bacteriophage infection (=vector). >Top Evolutionary organelle: Bacterium is a single cell organism; is a type of asexual reproduction. Recent biotechnology clarified mutual exchange of genes between bacteria; by way of bacterial conjugation and via bacteriophage. (current selective breeding) Sexual reproduction of E. coli: 1946 Esther Lederberg found sex factor in E. coli, and called F-plasmid (F-factor, Fertility factor); allows genes to be transferred from one bacterium carrying the factor (male) to another bacterium lacking the factor (female) by conjugation. F factor is constitutive for transfer proteins due to a mutation in the gene finO. During conjugation, cells lacking the episome (F-, female) receives either the episome (F+) or the episome plus the chromosomal genes to which it is attached (Hfr cell) F+ cell: possesses F factor as a plasmid independent of the bacterial genome. F plasmid contain only F factor DNA and not DNA from the bacterial genome; makes sex pilus that joins donor F- cell: does not contain F factor and act as the recipients. Hfr (High-frequnecy recombination) cell: possesses the entire F episome integrated into the bacterial genome. F' (F-prime) cell: is formed by incorrect excision from the chromosome, resulting in F plasmid carrying bacterial sequences that are next to where the F episome has been inserted.

3. 動く遺伝子とバクテリア: drug resistance: 薬剤耐性 (insusceptibility or acquired resistance) >Top susceptibility: (薬剤が有効な)感受性 Shigella: 赤痢菌<志賀潔 1898発見 selective breeding: 品種改良 episome: エピゾーム 遺伝子の運び屋としてのファージ T2 Phage: バクテリアの雌雄区別: >Top Episome: one of extrachromosomal genetic elements (plasmids), consisting DNA and capable of conferring a selective advantage upon the bacteria. Episomes is attached to the bacterial cell membrane (F+) and Hfr cells act as donors (male) during conjugation in certain bacteria (Eg. Escherichia, Salmonella, Serratia, Pseudomonas) Fプラスミドの交配での移動: Transfer of F plasmid in mating:

>Top 4. Common Viruses of Human and Animals: Human history has been battles against pandemic. 541-c750: the 1st plague pandemic; from Egypt to Mediterranean and NW Europe. 14C; c1331-c1855: the 2nd plague pandemic (Black Death); from Central Asia to Europe (landed in 1348), 25 million (1/4 of then population) died, causing the end of serfdom and the Medieval age; decline of the absolute authority of Christianity. 16C: Syphilis caused by Treponema pallidum. 17ｰ18C: smallpox, tuberculosis 19C; 1817-1823: Cholera (Vibrio cholerae); originated from India, Ganges river; 1883 Vibrio cholerae was discovered by Koch; 100K died in Japan under unequal treaty. 19C: 1855-1960: the 3rd plague pandemic: from China to India, world, and west coast of US. There are specific medicine against bacteria, but no effective medicine (vaccine only) against virus. Eradication of infectious diseases: In 1980/5, WHO declared the eradication of smallpox. In 1796, Jenner found vaccination; when no one recognizes bacteria, virus or immune system. Common viruses of human and animals: Rabies virus: this virus infects not only dog, but also wild animals such as wolf, skunk, fox, mongoose, bat. Yellow fever: this yellow fever virus infects wild animals in a jungle and mosquitoes act as the vector agent. Japanese enchephalitis: this virus infests pig, horse, heron and other wild animals such as bat, snake, and mosquitoes act as the vector agent. >Top Hepatitis virus: there are many types of this virus: Type-A/B/C/D/E; here Type-A is epidemic hepatitis which can be recovered. Type-B is more serious, which is infected via blood transfusion from a carrier, where the virus infects (horizontally and vertically) hepatocytes and develops liver cirrhosis and eventually liver cancer. This type-B carrier accounts more than 200M worldwide, of which 80% are in Asia. The 75% of all hepatitis carriers are this type-B. Japanese Type-B carrier is 10time higher (about 2-3M carriers, and 20K liver cancer patients) than that of US and Europe. Type-C is also cancer virus. Type-B hepatitis virus cannot be incubated in vitro; only incubated by chimpanzees. There are many HBs (hepatitis B surface) antigens attached on the surface of Type-B virus; this HBs antigen could be used as a vaccine against the virus. Mass production of HBs antigen can be possible by biotechnology; to use another virus as a vector of HBs antigen producing gene into Type-B hepatitis virus. As Type-B hepatitis virus infects only human and chimpanzee, which might be the common organelle held by the common ancestor of human and chimpanzee. >Top Human cancer virus (Five kinds) 1) Type-B/C hepatitis virus: 2) EB (Epstein-Barr) Virus: Human herpesvirus 4 (HHV-4) is one of the nine human herpesvirus types. NPC (Nasopharyngeal Cancer): mostly south China and partly SE Asia. It is not clear either genetic factor or Environmental factor affects this NPC; the former factor is believed to affect more estimated by medical anthropology (high racial sensitivity) People who speak Southern Min language (of southern Fújiàn), Hakka language (HK, Taiwan), and Cantonese (Guǎngdōng); who live as overseas Chinese in Singapore are descendants of these three people (South Mongoloid). 3) ATL (Adult T-cell leukemia) Virus: Leukemia is a cancer of blood: cancer of immune system's T-cells, caused by human T cell leukemia virus type-1 (HTLV-1). ATL virus carriers are mostly in Kyushu or Okinawa of Japan (dweller of ancient Japan). Only 1/2000 of the carriers cause leukemia. ATL virus infect not only human but Japanese macaque (monkey); the latter distribute in all Japan. >Top ATL virus is a member of retroviruses (RNA virus), and is Oncovirus that can cause easily cancer (called cancer virus). 4) HPV (Human Papillomavirus): cancer of cervix, vulva, vagina, penis, anus, mouth, throat; spread through sexual contact. 5) HIV (Human Immunodeficiency Virus): In 1981, the first HIV is recognized in Los Angels; HIV made the jump from other primates in west-central Africa in 20C. HIV is followed by a prolonged period with no symptoms. When the infection progresses, it interferes more with the immune system; developing candida, tuberculosis (Carini pneumonia), opportunistic infections, and tumors (Caposhi sarcoma), etc. (AIDS, Acquired Immunodeficiency Syndrome) HIV is spread primarily by unprotected sex, blood transfusions, hypodermic needles, and from mother to child. HIV is a member of retroviruses (RNA virus); is Lentivirus characterized by long incubation periods. there is no cure or vaccine; but antiretroviral treatment can slow the course of the disease; without treatment, the average survival time if 11 years.

4. ヒトと動物の共通ウイルス: syphilis: 梅毒 smallpox: 天然痘 <largepox=syphilis; smallpox and measles exported from Europe to America, while syphilis from America to Europe by Columbus. EB 人類の歴史は伝染病との闘い 14C: ペスト(黒死病) 欧州の中世の終わり 16C: 梅毒 17-18C: 天然痘・発信チフス Jennerの種痘 (1796) 19C: コレラ・結核 不平等条約下の日本での大流行 20C: インフルエンザ Size of microorganism: 100-10μm: 原虫・真菌 10-1μm: 細菌 1μm-100nm: rickettsia 100-10nm: virus 光学顕微鏡分解能以下 10-1nm: polymer 1nm-1Å: molecule 1Å- : atom 人畜共通ウイルス; 進化性オルガネラ 水平感染 (同一種内、異種間) 垂直感染 (子孫へ継承)     ヒト発癌ウイルス (5種): B型/C型肝炎ウイルス 日本B型肝炎キャリア3M人、肝臓癌患者は20K人 表面にHBs抗原あり ヒトとチンパンジーのみ感染 EBウイルス (上咽頭癌等) ヒトの癌ウイルス第1号 南方モンゴロイド(南方中国等、闽南･客家･广东)に人種的感受性 →遺伝人類学 環境因子より遺伝因子的 ATL (成人T細胞白血病) 白血病は血液の癌 2000人キャリアの内1人白血病 九州と沖縄(日本の先住民族)に多い レトロウイルスで、発症が早いオンコウイルス HPV (ヒトパピローマウイルス) HIV 1981に米国で発見 治療法･ワクチンないが８延命薬あり; ART(antiretroviral therapy) 世界のHIV38M人、 日本のHIV21K, AIDS患者9K レトロウイルスで、発症が遅いレンチウイルス Winie Byanyima, Executive Director of UNAIDS published: 2020, HIV and Covid-19: "This is a unique opportunity to reimagine systems for health: All eyes are on health, health systems and health care, with countries wanting to be better equipped to deal not only Covid-19 but also to create healthier, more resilient societies. We can seize this opportunity by learning from HIV an from Covid-19 to maker important changes to develop rights-based, equitable, people-centered systems for health. "

>Top 5. Deadlock of Darwinism: 1859/11: Charles Darwin published 'On the Origin of Species': the diversity of life arose by common descent through a branching pattern of evolution, presenting evidence from the Beagle expedition in 1930s and his subsequent findings; causing controversial about the transmutation of species from Church of England with the beliefs that species were unchanging parts of a designed hierarchy and humans were unique. Summary of Darwin's Theory: Every species is fertile enough, the population would grow (fact). Despite periodic fluctuations, populations remain roughly the same size (fact). Resources are limited and are relatively stable over time (fact). Struggle for survival ensues (inference). Individuals in a population vary significantly from one another (fact). Much of this variation is heritable (fact). Individuals more suited to the environment are more likely to survive and leave heritable traits to future generations, which produces the process of natural selection. These variations accumulate over time to form new species (inference). Questions to Darwinism: Is it possible that the excellent or adapted individuals really appear? Is it probable that the individuals with less adapted are weeded out or died out, and the ones with more adapted survive? Does it really happen that a big change such as the birth of new species occur by accumulations of individual changes caused by small mutation and natural selection? (here, mutation should be gene mutation, which is heritable.) Is the Theory consistent with the facts shown by many fossils?

5. 破綻したダーウィニズム: Drosophila: ショウジョウバエ synusium: 種社会, 分層群落, a structural unit of ecological community characterized by relative uniformity of life-form Darwin進化論への疑問: ランダムな突然変異によって優れた個体、適者が実際に出現するか 突然変異=遺伝子の突然変異=形質が遺伝するか 突然変異を起こすとほぼ死亡。適者の例は圧倒的に少ない。音楽に雑音混入ではないか 劣った性質は淘汰され、優れた性質を持つ個体は生存できる確率は大きいか 適者生存ではなく運者生存ではないか (魚の幼魚の例) 小さな突然変異と自然淘汰による個体変化の積み重なりで、新種誕生ができるか 無数の変化は整然と行われない (爬虫類→鳥類への変化) 化石との整合性と合うか 生物変化の移行期の化石は発見されていない (missing link)

>Top Comparison of Darwin's Theory vs. Kinji Imanishi's Theory:   K. Imanishi's Theory Darwin's Theory Common ancestor agree agree Level of evolution species, synusium individual Cause of changes certain directional change by unknown mechanism mutation Generation & fixation of species negation of natural selection and living density by segregation survival of the fittest and branching due to natural selection Methodology organically harmonic societies of species (macroism) theory of individual level (reductionism, or microism) Opportunity of theory formation discovery of segregated life of larva of Ephemeroptera (dayfly) idea from artificial selection by breeding Unsolved portion mechanism of a certain directional evolution tautology of 'adaptation'; jump of evolution by mutations¯ Origin of life no mention no mention Kinji Imanishi (1902-1992): Japanese ecologist and anthropologist; found of Kyoto University's Primates Research Institute. Viewpoint of Imanishi's Evolution Theory: There are now about 1.3M species on this earth, occupying at each ecological niche. This fact indicates each species is trying to expand its own living space, rather than to destroy its competitor or be destroyed by it. There has been coexistence of various species composed of irregularly evolved individuals; for example, some reptiles remain crawling on the ground, and some reptiles evolved their forelimbs into wings in rather short period (say, several hundred thousand years) Darwinism refers to the breeding of plant by gardeners; and insists nature instead of breeders performs artificial selection. (natural selection). But actually, the selection will not change the species; thus Darwinism induced 'mutation' into its theory to change the species. But the mutation causes in vast majority cases negative results of malformation or death of the individual. In evolution, the species as a whole seem to evolve to a certain direction in the longer period, though the change individual levels are varied. Neo-Darwinism adopts the idea of reductionism, whose methodology attained remarkable success in physics and chemicals; but it seems difficult to apply it to evolution and biology.

>Top 6. The Birth of Viral Evolution: Punctuaed equilibrium: In 1972; Stephen J. Gould and Niles Eldredge published punctuated equilibria theory, proposing that degree of gradualism attributed to Charles Darwin is contradictory to the fossil records. Once a species appears, the population will become stable, showing little evolutionary change for most of its geological history. (stasis) Rapidly evolving peripherally isolated populations may be the place of origin of may evolutionary novelties. Isolation and small size may explain phenomena of rapid evolution. cladogenesis; which occurs when there is branching, leading to two or more lineages and resulting in separate species. anagenesis: gradual evolution of a species that continues to exist as an interbreeding population. Species Extinction: 1.3M species on the current earth; 1M animal species (0.75M are anthropoid), and 0.3M plant species. The number of extinct species are estimated 100 times of the current living species; i.e., existed 130M species. Two patterns of species extinction: 1) extinction caused by drastic change of environment. dynamic changes of environment became clear by geological evidence (mass extinction; Big Five extinction events; O-S (End Ordovician, 444ma, 86%); newly expose silicate rock sucked CO2, chilling planet; Late D (Late Devonian, 375ma, 75%); algal blooms sucked O2, suffocating bottom dwellers like trilobites. P-Tr (End Permian, 251ma, 95%); the worst extinction ever seen, nearly ended life on earth; a potent greenhouse gas; oceans acidified and stagnated, belching H2S. Tr-J (End Triassic, 200ma, 80%); no clear cause has been found. K-Pg (End Cretaceous, 66ma, 76%); the asteroid impact ended dinosaurs' reign. 2) extinction wiped out by formation of new species. It has been explained that battles occurred between the new species and the old ones, and the old ones were wiped out; but it is possible for the old ones to survive in different places; or even coexistence could be probable. Neanderthal: appeared about 90K years ago and were extinct 35K yeas ago. What was the reason of sudden extinction; was it by the battle with Homo Sapiens, or by environmental change? One possible answer is a kind of transformation form Neanderthal to Homo Sapiens, probably caused by DNA transfer. >Top Constant directional change: Increase of brain capacity: about 600 CC of Australopithecus to 1350 CC of Homo Sapiens in 4M years. Becoming intelligent: by 1) upright bipedal walking, 2) change from forefoot to hand, 3) development of brain >Top Neoteny: puberty: monkey 2 years, Chimpanzee 9 years, human 13 years neoteny of human: acquired learning is particularly important. gene change by virus is basically orderly; transferred gene is definite and the virus delivers the gene to a certain place of host DNA, which suggests more directional evolution. thus constant transfer of definite genes from a certain virus during longer neoteny period can well explain human evolution.

6. ウイルス進化論の誕生: Punctuated equilibrium: 断続平衡説 stasis: 均衡状態, a period or state of inactivity or equilibrium. clade: 分岐群, a group of organism with a common ancestor cladogenesis; an evolutional splitting into two distinct species, forming a new group of organisms (=clade) anagenesis: species formation without branching of the evolutionary line. speciation: 種形成, formation of new and distinct species developmental biology: 発生生物学, study of process; how animals & plants grow and develop; enocompasses regeneration, asexual reproduction, metamorphosis, and growth and differentiation of stem cells. neoteny: 幼形成熟, retention of juvenile features in the adult animal. puberty: reach sexual maturity Punctuated equilibrium, 断続平衡説 (区切り平衡説) 新たな種は地質学的瞬間(約10万年)に形成される 種の変化を示す中間駅な化石が発見されない。 種の形成も種の絶命と突然発生 (弾速的かつ急激に） 地球史上の大量絶滅事件 (Big Five絶滅) ネアンデルタール人は約3万年前に絶滅。 ウイルスによる遺伝子の変化: 運ぶ遺伝子はある決まった遺伝子 ウイルスが持ち込む宿主の遺伝子の場所も特定している 人の成熟は、ウイルスの影響を継続的に受ける (長いネオテニー期間) →人の定方向の進化の理由

>Top 7. Forecast from Viral Evolution: Definition of Species: a set of animals or plants in which the members have similar characteristics to each other and can breed with each other. Imanishi's Evolution theory expanded this definition to 'Specia', which means species society; not only individuals related by breeding, but include the partial society of living creatures. Species tend to be conservative to maintain the belonging species society. >Top Transfer of genes is not limited to the collection of reproductive individuals; it became clear that virus can transfer genes beyond species. (superspecia=the total species which can transfer genes via vertical and horizontal transfer) Eg. other animals except human and Japanese monkey cannot synthesize vitamin C in the body. The nature of virus is not to cause infectious diseases, but cause evolve species in superspecia. Plasmid of bacteria can transfer drug resistance gene to bacteria via its pilus, while virus is an intense organelle which can proliferates within the host cell, and can transfer genes beyond space and species. and space. All animals have various viruses, which assist to make the host animals evolve to a certain direction, in some cases drove the host to extinction. In some major extinction events occurred in the earth history, infectious diseases by viruses may be the real cause. Virus Evolution Theory: Neo-Darwinism attributes the change of genes to mutation. But Virus Evolution Theory consider it is caused by horizontal transfer of genes by a vector (plasmid and virus). Biotechnology proved to enable to make supermouse; which might have occurred in the case of giganticness of dinosaur. >Top ERV (Endogenous Retrovirus): about 12% of mammals' genome are derived from ERV. (Virus fossil); this shows the ancestor of mammals were infected by enormous retroviruses. Transposon: a segment of bacterial DNA that can transfer another place on the genome. (called jumping gene) Similarity of DNA between human and bacterium (Pseudomona K-62): mentioned below↓: Viral diseases will increase: Measles: highly contagious infectious disease by measles virus; causing fever, cough, runny nose, and inflamed eyes, red flat rash spreads on the body. No specific treatment is available, but supportive care only. The measles vaccine is effective to prevent the disease, and is delivered in combination with other vaccines. Vaccination resulted in 80% decrease in deaths now. Smallpox: infectious disease caused by two virus variants, variola major and variola minor. In 1980, WHO certified the global eradication of the disease. The risk of death was about 30%; with extensive scarring of skin, some were left blind. In 15-17C, Spanish delivered this disease from Old World to America during the conquest of Aztecs and Incas In 18C Europe, about 400K people died from the disease per year, killed up to 300M in 20C. 1796, Edward Jenner, pioneered to create smallpox vaccine. In Jenner's time, smallpox killed around 10% of population. He observed that milkmaids were generally immune to smallpox (cowpox). Yellow fever: This is common in tropical Africa and spread to South America. caused by yellow fever virus (RNA Flavvirus); symptoms include fever, chills, loss of appetite, nausea, muscle pains, then liver damage begins causing yellow skin. It infects only humans and other primates and several mosquitoes. A safe and effective vaccine exist. Without this vaccine, the construction of Panama canal could not be succeeded. Japanese encephalitis: This disease was first described in Japan in 1871, which is an infection of the brain caused by JEV; symptoms include headache, vomiting, fever, confusion and seizures, which occur 5-15 days after infection. JEV is generally spread by mosquitoes (specifically Culex type). Pigs and wild birds serve as a reservoir for the virus. prevention is with JE vaccine, which is safe and effective, as well as avoiding mosquito bites. Once infected, no specific treatment with only supportive care. Poliovirus: Infantile paralysis is a serotype of Entervirus C, composed of RNA genome having icosahedral symmetry, first isolated in 1909. Poliovirus is a simple and well-charactrized viruses, which become a model system to understand the biology of RNA viruses. is a highly infectious viral disease particularly under 5 years of age, and is transmitted by person-to-person spread, or by common vehicle (water or food) and multiplied in the intestines from where it can invade the nervous system and cause paralysis. Wild poliovirus cases have decreased by over 99% since 1988. US President Roosevelt was infected this disease and was forced to fight against illness. >Top Spanish flu: in 1918-20; caused by HiN1 influenza A virus; infested 500M people. The death was estimated 50M, or as high as 100M. It triggered a cytokine storm (immune system caused uncontrolled excessive release of signaling cytokines) Asian flu: in 1957-58; caused by influenza A virus subtype H2N2, originated in Gùizhōu, China, died 1-4M people. the virus was most deadly in pregnant women, elderly with pre-exisiting heart and lung disease. Recent cancer viruses, such as EB virus, Human papillomavirus (HPV), ATL virus, Ebolavirus, Human Immunodeficiency Virus (HIV) are continuously recognized. Disease-causing viruses are mutants or failures; their primary role is to deliver horizontally genes which cause evolution to the host.

7. ウイルス進化論からの予言: endogenous retrovirus (ERV): 内在性レトロウイルス LUCA: Last Universal Common Ancestor: 最終共通祖先 Pseudomonas K-672: 水銀耐性菌 mercuric reductase: 水銀還元酵素 glutathione reductase: グルタチオン還元酵素 Japanese enchephalitis (JE): 日本脳炎 superinfection: 重複感染, second infection superimposed on an earlier one, following treatment with broad-spectrum antibiotics. Viral Infections: Type of virus Infection DNA virus Herpes virus (HSV)     Cytomegalovirus (CMV) salvary gland, kidney, lymphocyte   EB virus lymphocyte (B cell)   Herpes simplex virus skin, nerve   Herpes zoster virus nerve Adenovirus     Human adenovirus intestine, upper trachea RNA virus Enterovirus     Poliovirus intestine   Coxsackie virus skin Rhinovirus upper trachea Retrovirus     AIDS virus lymphocyte (Tcell)   ATL virus lymphocyte (Tcell) ウイルス病は今後も増える: 歴史を動かした伝染病 麻疹 天然痘: 藤原氏4兄弟死亡→法隆寺夢殿建立 スペインの南米征服に利用 18Cジェンナーの種痘発見 黄熱秒 野口へ出よ 日本脳炎 東アジア、東南アジア ブタなどに常在 ポリオウイルス 小児麻痺発症 血液経由で運動神経破壊 ルーズベルト大統領も感染 狂犬病 スペイン風邪 1918-20; 第一次大戦戦死者以上 50-100M人死亡 アジア風邪 1957-58; 東アジアで流行 1-4M人死亡 EVウイルス 上咽頭癌 パーキットリンパ腫 ヒトパピローマウイルス 皮膚癌, 子宮頸癌 ATLウイルス 成人T細胞白血病 エボラ出血熱 アフリカ発祥、高い致死率 エイズウイルス 世界的な流行 病気を起こすウイルスはミュータント、出来損ない 本来の役割は、進化を起こる遺伝子の水平移動

>Top Amino acid sequence: human and bacterium (Pseudomona K-62) 1) Bacteria: Thr- Ile -Gly-Gly-Thr-Cys-Val-Asn-Val-Gly-Cys-Val-Pro-Ser-Lys- Ile -Met (mercuric reductase portion) 2) Human : Lys- Leu-Gly-Gly-Thr-Cys-Val-Asn-Val-Gly-Cys-Val-Pro-Lys-Lys-Val-Met (gutathione reductase portion) Asn=Asparagine; Cys=Cysteine; Gly=Gycine; Ile=Isoleucine; Leu=Leucine; Lys=Lysine; Met=Methionine; Pro=Proline; Ser=Serine; Thr=Tyrosine; Val=Valine; Similarity of the above 1) and 2) indicates both genes have common origin; once some virus horizontally may have delivered the gene between bacteria and human. This 1) gene making mercuric reductase can be found on a plasmid of Escherichia coli. Some day, a new book titled 'Origin of human genes - human evolution by change of genes via virus vector' will be published.

>Top 8. Is the Criticism of Darwinism Taboo? In 1959, when Charles Darwin published 'On the Origin of Species,' supported by then well-known biologist Thomas H. Huxley, late was called 'Darwin's Bulldog.'; in 1860 strongly argued with Samuel Wiberforce about evolution such that human descent from apes. Darwin himself was a devout Christian; saying "I have never been an atheist denying the existence of God. An agonistic would be the most correct description of my state of mind." Huxley was slow to accept Darwin's gradualism and natural selection, but he fought against the more extreme religious tradition. Huxley elaborated agnosticism; "Human reason is incapable of providing sufficient rational grounds to justify either the belief that God exists or the belief that God doe not exist." Darwin firstly and logically explained the process of evolution by two concepts of survival of the fittest and natural selection. But Church of England argued that miracles broke God's laws, so belief in them was atheistic. In 1925/7, Scopes Monkey trial: State of Tennessee vs. John Thomas Scopes high school biology teacher John Scopes was charged with illegally teaching the theory of evolution in violation of a state law. Then the charismatic Bryan led a movement to ban the teaching of evolution from classrooms in US. Of 15 states with anti-evolution legislation pending in 1925, only two states (Arkansas and Mississippi) enacted laws restricting teaching of Darwin's theory. The judge delivered a verdict of guilty and fined Scopes $100. Darwin discovered natural God in the world of biology, a beautiful theory God created. But scientists gradually began to believe that it is more important to pursue how natural laws function rather than to proved who made the natural laws. Also Darwin seemed to feel some uncertainty that natural selection depended by accidents. Social Darwinism: Since 1870s, Western nations claimed to apply Darwinism to sociology, economics and politics. Such view stress free competition between individuals in laissez-faire capitalism and struggle between national or racial groups, which supports relentless exploitation and the conquest of the weak by the strong; regarding natural selection as free competition, and survival of the fittest as legitimacy of winner takes all. Biologists appealed that Darwinism is merely intended to describe biological phenomenon and not to imply this phenomenon be used as a moral guide in human society. Western powers gained theoretical support for their colonialism; the ruler is the fittest, i.e., the blessed race, or the Union Jack.

8. ダーウィニズム批判はタブーか: agnosticism: existence of God or supernatural is unknown or unknowable 1871 caricature the descent of man: 植物学者Thomas H. HuxleyはDarwin弁護に奔走 キリスト教界を代表したSamuel Wiberforceと大論争 DarwinもHuxleyも不可知論の立場 1925米国テネシー州の進化論裁判 John Scopesは、ハイスクールで進化論を教えたとして告訴され$100の罰金刑 1982年の連邦地裁が違憲判決 ダーウィン進化論の起源はキリスト教 自然の中に神の創った美しい法則を見出す ダーウィン的社会進化論: 資本主義における自由競争=自然淘汰、人生の富と名誉の成功者=適者生存=恵まれた種族 植民地征服の理論的支柱

>Top 9. Why Human Beings Evolve? View of Imanishi's Theory: summarized by Pamela J. Esquire, Canadian anthropologist, in 2007. Kinji Imanishi (1902-92), entomologist, ecologist, anthropologist and founder of primatology in Japan. In 1940, he published his first and best known book, Seibutsu no Sekai (The world of living things); whose opening passages begins 'how diversity came to exist on earth.' >Top His basic view emphasized cooperation rather tan competition in the natural world.; 'lifestyle partitioning" among coexisting species.; completely different world for different life forms. His concept of 'species society' or 'specia.' He had discussed the micro-environment around each species and each individual, and the organism's effect on its micro-environment. Consider the community of microbes, fungi and invertebrates that inhabit the root zone of plants. Each plant and its associated fauna can be regarded as a local ecosystem, whose members interact primarily among themselves and withe the physical environment in the immediate vicinity of the plant. all the differences of living things that separate them from nonliving things fade at the point where life came from nonlife and rudimentary living forms emerged from the physics and chemistry of the early-Earth atmosphere. Imanishi's contention that 'when it comes time to change all individuals will change' appears similar to the idea of selection of whole population; competition in the natural world is largely wasteful so that organisms are more likely to avoid it. We view the population system, whether intraspecies or interspecies, as a biological entity of fundamental importance. While, in 1985/10: Bervery Halstead, British paleontologist, introduced Imanishi Evolution theory at Nature titled 'Anti-darwinian theory in Japan.' with subtitle of 'The popularity of Kinji Imanishi's writing in Japan gives an interesting insight into Japanese society.' describing: Imanishi sees the group and not the individual as of fundamental important in evolution, he does not see struggle in nature but rather the underlying harmony. Darwin assigns to the role of the individual, especially with regard to the concept of natural selection, involving competition among individuals in the struggle for existence. what determines survival is purely accidental. It is a matter of luck rather than selection. Imanishi sees the species or more properly species-society as being an entity in its own right. All the individuals of a species change at one when the time change comes. Imanishi chose habitat segregation and an evolutionary theory based on the principle of cooperation and mutualism. Imanishi's evolution theory is a poetic vision, it is beautiful to contemplate but it is a dream and it is Japanese in its unreality. There is no longer any foundation for Imanishi's attack on what he imagined Darwinism to comprise - it was merely a caricature of Darwin. Drug resistant bacteria are not evolution. In Japan frequency of appearance has decreased to one third from 1972 to 1979. This mainly due to the mercury pollution control in Japan. Consumption of Mercurochrome (=merbromin, organomercuric disodium salt) which is no longer sold in major countries. After discontinuation of this Mercurochrome, mercury resistant bacteria drastically decreased. Similarly streptomycin resistant bacteria decreased by changing the use of streptomycin. These phenomena show that appearance of drug resistant bacteria are reversible adaptation, not irreversible evolution. the case industrial melanism of Biston betularia (peppered moth) shows that the color is returning to the original while color according to the environmental cleanup. The Virus Evolution theory is still in the process of development, because evolution itself could not yet fully understood by modern biology, which is particularly weak in discontinuous phenomena; but this theory could well explain the following four points which Darwinism could not. Abrupt change of species Abrupt extinction of species Evolution to a certain direction Parallel evolution There are many difficult and unknown areas of discontinuity; such as weather forecast, :

9. ヒトはなぜ進化するのか: entomologist: 昆虫学者 lifestyle partitioning: 棲み分け species society =specia: 種社会 arcane: understood by few, mysterious epigenetics: heritable phenotype changes that do not involve alterations in DNA sequence <epi- outside of; by environmental factors; Eg. such as methylene and histone modification, non-genetic factors cause the organism's genes to behave differently. DNA methylation: Methyl group can tag DNA and activate or repress genes. Histone modification: the binding of epigenetic factors to histone tails alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated efficacy: the ability of produce a desired result orangutan: oran+utan, forest man altruism: 利他主義 ⇔egoism contention: 論点, assertion Biston betularia=peppered moth, オオシモフリエダシャク calcinogenic mechanism: 発癌メカニズム 今西錦司理論=反ダーウィン進化論: 英国Nature誌に、日本における反ダーウィン説を皮相的に紹介。 Beverly Halsteadによれば、今西進化論は、競争より協調に基づく非合理的感傷に満ちた夢物語。詩的なビジョンと日本的な非現実性と要約した。 進化の単位は個体でなく種である 種が共存するための棲み分け現象 ウイルス感染による遺伝子の水平移動 ほとんどの個体が感染し、種全体として短期間で同じ遺伝子の影響を受ける 自然淘汰は進化は存在しない。 適応は進化ではない。 進化は不可逆的 ウイルス進化論はダーウィン進化論で説明できない点を説明できる 種の急速な変化 種の急速な絶滅 定向進化 平行進化 不連続性に弱い近代科学 天気予報 発癌メカニズム、 個体発生の気候 触媒作用 超電導メカニズム

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During staying home to avoid infectious Covid-19, various writings about viruses are very interesting and exciting. I have believed Darwin's Evolution theory just like Newton's theory, because both can well explain phenomena observed daily life. But the Virus Evolution theory (written in 1996) awakened me up; it it attractive to know the function of viruses, which seems not only vicious enemies to cause serious diseases but old friends to make us evolve.

コロナウイルス感染を避けるための自宅待機中のウイルスに関する読み物は興味深い。 ダーウイン進化論は、ニュートン理論のように日常生活をうまく説明できると信じていた。 だがウイルス進化論 (1996)には驚いた。ウイルスの役割は、深刻な病気を引き起こす敵というだけでなく我々を進化させる古い友達のように見えるということである。