Appendix 1*) For Essential Information Very Well Illustrated in Google and Wikipedia

256 Pages·2016·2.19 MB·English

Appendix 1*) For Essential Information Very
Well Illustrated in Google and Wikipedia
*) in Support of the Text with Literature Citations. Referrals to illustrations in
Appendix 2.
CancerinthePlant.TheinsertionoftheAgrobacteriumtumefacienscircularplasmid
T(transferred)DNAintothegenomeofitsnewhost,theplant(GelvinBS.Microbiol
Molecular Biol Rev 2003;67:16–37). The plant cancer “crown gall” (agrocallus;
Agrobacterial crown gall) consists of malignantly transformed cells replicating the
agrobacterialTDNAplasmid(reviewedinpostscriptTableXXXV).Forreference:
Koncz C Mayerhofer R Koncz-Kálmán Zs et al EMBO J 1990;9:1337–1346.
Transferofpotentiallyoncogenicbacterialgenesandproteinstopatients:Septicemic
Bacteroides enterotoxigenic (Sinkovics J G & Smith JP Cancer 1970;25:663–671;
ViljoenKSetalPLoSOne2015;10(3):e0119462);Bartonellabacilliformisetc(Guy
LetalPLoSGenet2013;9(3):e1003393;HarmsA&DehioCClinMicrobiol Rev
2012;25:42–78;LlosaMetalTrendsMicrobiol2012;20:355–9;MinnickMFetal
PLoSNeglTropDis2014;6(7):e2919);Helicobacterpylori(BonsorDAetalJBiol
Chem 2015;pii:jbc.M115.641829; Su YL et al J Immunol 2015;194:3997–4007;
VaziriFetalPathogDis2015;73(3).pii.ftu021);Porphyromonasgingivalis(KatzJ
etalIntJOralSci2011;3:209–215);TuberculousinfectionswithA.tumefaciensin
patients(RamirezFCetalClinInfectDis1992;15:938–940).
DNA-bindingAntibodies.DNA-(orRNA-)bindingproteinsusezinkfingermotifs,
leucine zippers and winged (beta-sheet loops) helix-turn helix motifs (HTH, two
helices separated by the loop, RNA/DNA-binding domains) in recognition of
RNA/DNA receptors for attachment. Pro-apoptotic protein p53 is commonly
attached to DNA (vide infra). Advanced multicellular organism established a
fundamental relationship between DNA genes and circulating antibodies, which
overlappedthepre-existingmiRactivityforposttranslationalgeneexpression.One
of the best examples is played out in the pathogenesis of the T cell lymphoma
mycosis fungoides and Sézary syndrome (that may also hide the underlying
retroviral pathogen/passenger presumed to be there by Dorothea Zucker Franklin)
(ProcNatlAdadSci1991;88:7630–7634;1997;94:6403–6407).Oneoftheinducer
oncogenes of mycosis fungoides is TOX (thymocyte selection-associated high
mobility group protein box gene), which normally regulates T cell differentiation.
©SpringerInternationalPublishingSwitzerland2016 559
J.G.Sinkovics,RNA/DNAandCancer,DOI10.1007/978-3-319-22279-0
560 Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia
Overexpressed TOX induces mycosis fungoides tumor cell proliferation and
migration. The TOX protein mRNA is under the control of miR-223 through
specificdomainalignmenttoits3′UTR(untranslatedregion)intheAGOcomplex.
HighbloodlevelsofmiR-223bringaboutthecessationofmycosisfungoidestumor
cell growth. The production of tumor initiator high mobility group
(HMG) DNA-binding protein is targeting its own DNA genes of T cell dediffer-
entiationandhoming;itisswitchedoffbyaspecificmiR(HuangYetalOncotarget
2014;5:4418–4425; McGirt L et al J Invest Dermatol 2014; 134:1101–1107;
O’Flaherty E & Kaye J BMC Genomics 2003;4:13).
ContinuousReplicationoftheTrypanosomainliquidmedia.Notintheinsect’sgut,
but in the blood stream of its mammalian host, the slender Trypanosoma cell is fed
primarilyonsugar.Thisprotozoanisalsocapabletosynthesizeglucose-6-phosphate.
Growing invitro insuspension, its speed ofreplication isdependentonthe concen-
trationofsugarintheliquidmedia.Thestressresponsiveheatshockproteins(Hsp90)
workincellsurvivalpathwaysintheprotozoa,butbecameoncoproteinsinmulticel-
lular,incl.human,hosts.Questionsstillincompletelyanswered:Intherapidlygrowing
T.brucei,sugarmetabolismiswarburgian?Insulin-likegrowthfactorreceptor(IGFR)
is overexpressed? Hsp90 promotes growth; is there growth dependence on Hsp90?
Intranuclear Ki-67 is overexpressed? Telomers are capped after each cell division?
Hsp90 inhibitors (geldanamycin analogs) induced trypanosomal death due to heat
shock.Positiveanswerswouldmeanthattheunicellularprotozoan’srapidgrowthis
comparable to that of a cancer cell. Cooperative studies of Ludwig Maximilian
University (LMU); Institut National des Sciences Appliqueés (INSA), Université
Toulouse;CentreNationaldelaRechercheScientifique(CNRS),UniversitéBordeaux.
AllmannSetalBiolChem2013;288:18494–18505.VanReetNetalExpParasitol
2011;128:285–290. Meyer KJ & Shapiro TA J Infect Dis 2013;208:489–499 http://
www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-department/parasitology; http:/
phys.org/news/2013-07-parasite-sugar.html; http://www.ncbi.nlm.nih.gov/pubmed/?
term=trypanosoma+liquid++culture Faculty Biology, Ludwig-Maximilians-
Universität München; Biozentrum, Grosshadernerstrasse 2–4, D82152 Martinsried,
Germany.TheJohnsHopkinsUniversitySchoolofMedicine,Baltimore,USA.
Stem Cells Ascend from the bottom of the Lieberkühn crypt to renew themselves
and release somatic cells to function as epithelial cells of the mucous membrane
(reviewed in Table I).
S.YamanakaLentivirallyTransferredfourstemcellgenes(oct4;sox2;klf4;c-myc)
for reprogramming human differentiated cells into pluripotential stem cells;
re-differentiationofpluripotentialstemcellsintodifferentiatedcellcouldbeinduced.
http://syntheticdaisies.blogspot.com/2012/10/the-spawn-of-gurdons-frogs.html.
Dictyostelia amoebae.TheAmoebozoanDictyosteliumdiscoideumexistsinmany
lifeforms:insexualcycle,invegetativecycle,andinsocialcycle.Itsdiscoidinisa
fibronectin; its tiger genes encode histocompatibility complexes; it uses
Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia 561
ERK/MAPKK signaling “cell survival pathways” (extracellular signal regulated
kinase; mitogen-activated protein kinase kinase). MAPKK becomes a
proto-oncogene in vertebrate mammalian (human) cells: in ras- (rat sarcoma)
transformed cancer cells. Members of the D. discoideum clade (D. purpureum, D.
fasciculatum)arecomparableintheirgenomicsandproteomics.Evolutionarilythey
separated from their common ancestor 600–800 mya and in comparison to the
yeast, doubled their number of protein-coding genes up to 12,000 (Loomis WE
Methods Mol Biol 2013;983:39–58). The other social amoeba, Acytostelium sub-
globosum emerges as a different species, which increased its chromosome number
upto18,butnotbecauseithasbecomediploid.ThestarvingD.discoideumformsa
conditionally multicellular fruiting body with spore ball on a stalk. It is the
migratoryslugcellsthateitherformthefruitingbodyorthestalk.Thefruitingbody
represents the germ cells and the stalk consists of the terminally differentiated
somaticcells.TheA.subglobosumdoesnotdifferentiateitsstemcellstoastalk;its
stalk is a-cellular. The cellulose synthase gene builds the cell-free stalk. If “The
differentiation of mortal or sacrificed somatic cells from reproductive germ cells
wasthekeyeventfortheestablishmentanddiversificationofmulticellularsystems”
(Urushihara H et al BMC Genomics 2015;16(1):80), then D. subglobosum should
be regarded evolutionarily more ancient than D. discoideum. A. subglobosum and
D. discoideum are casting light to the beginning of a decisive process in the
developmentofmulticellularity.TheDd-MRP4mitochondrialribosomalproteinis
able to induce in human cancer cells the process of programmed cell death
(apoptosis). Mitochondrial ribosomes are of ancient bacterial derivation. The
Dd-mrp4 gene product protein in D. discoideum is the major initiator of cell dif-
ferentiation (induced by starvation). Differentiation induction is achieved by the
Dd-MRP4proteinthroughitsentryintothenucleusforactivationofitstargetgenes
(miR genes?). Another unrelated and different D. discoideum ribosomal protein is
S4 (Dd-RPS4). It is homologous to the human chromosome X-linked cytoplasmic
ribosomal protein S4 (Hs-RPS4X) in 66% identity and 92% similarity in their aa
sequence (Maeda Y Biomolecules 2015;5:113–120).
AmphioxusI,prominentamongthemisBranchiostomafloridae.Possessesnotochord
and primordial nervous system consisting of intraabdominal sensory cells and
notochord nerve cells connected with axons and synapses. An advanced neuro-
chemical network releases and circulates cholinergic and GABAergic/glycinergic
(gamma aminobutyric acid) molecular mediators. The amphioxus’ achaete scute
homologues (Ash) exist conserved up to Homo (Lu TM et al Development
2012;139:2020–2030). The Ash genes may act as proto-oncogenes subject to
malignant transformation. The achaete scute homolog basic helix loop helix gene
(ash)andthedeltaligandNotchpathwayevolvedatthissite.Theadultamphioxus
preservesitsnotochord,whereastunicatelarvaeofCionalosetheircordatecharac-
teristics through metamorphosis into adulthood. The amphioxus frontal eye spot
revealsphotoreceptorJosephcellswithmanyhomologiestocamera-typelenseyesof
jawless (lamprey) to jawed (sharks) vertebrates (Candiani S et al BMC Neurosci
2012;13:59; Lu TM et al Development 2012;139:2020–2030; Vopalensky P et al
562 Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia
Proc Natl Acad Sci 2012;109:15383–15388). The amphioxus and the sponge
Amphimedon qeenslandica share an ancestral TGFβ gene (Song X et al Genomics
2014;103:147–153).AnadvancedmiRsystemcontrolsamphioxusgeneexpression
(ZhouXetalGene2012;508:110–116).Theamphioxusgenomepreservedinserted
six clades of non-LTR retrotransposons named among a long list of non-LTR ele-
mentsofothersourcesincludingthosefromCionaintestinalis(PermanyerJetalIntJ
Biol Sci 2006;2:48–53). The Lu TM team worked with B. floridae specimens col-
lectedintheTampaBay,Florida(W.P.Hallhttp://forums.about.com/ab-christianity/
messages?msg=10917.2462). As oncogenes, Ash induce esthesioneuroblastoma*),
medullarycarcinomaofthethyroid,smallcellundifferentiatedcarcinomaofthelung,
or transforms pre-existing adenocarcinoma cells into chemo-radiotherapy-resistant
neuroectodermal malignant cells (Wang XY et al Lab Invest 2007;87:527–539)
Single nucleotide polymorphism in the 3′ untranslated region of miRNAs
(hsa-miR-1827) occur in small cell lung cancers, in which the L-myc1 (1p34) and
achaete scute human homolog genes (11p15.1; 12q22-q23) are involved (Xiong F
etalCancerRes2011;71:5175–5181).
*)Esthesioneuroblastoma.Theorbitsandsinusescontainalarge,enhancing,and
expansilemassoccupyingtheethmoidaircells.Thecribriformplateisinvaded.The
left anterior cranial fossa is broken into. Preoperative platinum-based chemother-
apy,surgicalresection,andpostoperativeradiotherapyisthestandardtreatmentof
Hyams’highgradeandKadishadvancingstagetumors.FromMayoClinics:USA,
McElroy EA Jr et al Neurosurgery 1998;42:1023–1027; from Institut Gustave
Roussy, Villejuif, France, Modesto A et al Oral Oncol 2013;49:830–834; from
Children Hospital, Rabat, Morocco, El Kababri M et al Pediatr Hematol Oncol
2014;36:91–95. Comment: Treatedhigh grade tumorslie dormantand relapse.
Choanoflagellates (Monosiga brevicollis; ovata). Choanoflagellate genomic seg-
mentscontainingcellsurvivalpathwayPak(p21activatedkinase);whentransfected
into somatic cells of metazoan multicellular vertebrate hosts (mice; rats; human),
pak/Pak induces “malignant transformation” (Watari A et al Oncogene
2010;29:3815–3826). The merlin-encoding tumor suppressor gene neurofibro-
matosis NF2, the suppressor of cyclin D1 (or Bcl-1) promoter, is regulated by the
pak/Pakpathway.PAK1stimulatesthecyclinD1promoter;cyclinD1mRNAsrise.
Merlin inhibits the cell cycle in G1 by suppressing cyclin D1 and CDK4
(cyclin-dependentkinase)anddephosphorylatingtheretinoblastomaRBprotein.The
Rac/Pakaxisisanoncogene(XiaoG-HetalMolCellBiol2005;25:2384–2394).
Blooming Dinoflagellate Symbiodinium (zooxanthella) cells survive self-generated
toxins that are highly lethal to multicellular life forms up to fishes and Florida
manatees. ATP-cassette ABC transporter protein pumps expel the toxins by
mechanisms similar to those of tumor cells gaining resistance to chemotherapy
(Table I). Symbiodinium cells parasitize the cytoplasm of cnidaria corals, where
they are replicating very rapidly. There is a mass exodus of flagellated mastigote
Symbiodinium cells from the parasitized host cells. “Bleached” (whitened) coral
Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia 563
colonies are left behind. The motile mastigotes discard they flagellae and assume
non-motile metabolically quiescent coccoid morphology ranging in size of 6–13
μm.Bothmastigotesandcoccoidcellsundergo mitosis generating twomastigotes.
Dinoflagellates carry reticulated chloroplasts. The light-harvesting center is in the
thylakoid membrane; it contains a chlorophyll-protein complex. Symbiodinium
cells carry also mitochondria retaining some of their original genes. The intranu-
clear DNA is kept supercoiled within the chromosomes. In the S-phase of the cell
cycle, the uncoiled DNA duplicates. Symbiodinium cells rapidly replicate in cul-
tures inthelaboratory. Therapidlyreplicatinggenomesareofinterest: whatgenes
are constitutively activated? Are intranuclear Ki67 proteins overproduced? The
Symbiodinium genome operates over 42,000 protein-coding genes; duplicated
genes;basiceukaryoticandhorizontallyacquiredbacterialgenes.Itisspliceosomal
intron-rich: 18.6 introns / gene; its spliceosomal snRNA genes (U1-U6) are clus-
tered (Jeong HJ et al J Eukaryot Microbiol 2014;61:75–94; Shinzato C et al PLoS
One 2014;9(1):e85182; Shoguchi E Curr Biol 2013;23:1399–1408). In Summary,
some cnidarians carry virally infected endosymbiotic algae and respond with an
activeNFκB/STATpathway(inSinkovicsJGIntJOncology2015;47:1211–1229).
TiborGánti’sChemoton.Thechemotonisaself-reproducingautomaticmachinery;
itoperatesautocatalyticcyclesofchemicalsinaliquidbasesurroundedbyabilipid
membrane. Chemotons grow by metabolism and reproduce by biological fission,
but as non-genetic entities. Osmotic pressure within the microsphere (the chemo-
ton) induces invagination of the membrane leading to fission. The chemical reac-
tions within the chemoton are not dependent on enzymes. Divided chemoton units
are identical without hereditary variation. Cycle stochiometry characterizes math-
ematically and expresses quanitatively the chemical reactions occurring within the
chemoton. Incorporation of a new external molecule (molecule T) into the system
occurs through small gaps of the membrane. The amphipathic dynamic molecule
advances the internal metabolism of the chemoton toward the acquisition of heri-
tableenzymes(ribozymesbeingthefirst).Chemotronsaretheprimordialfirstcells
of the living matter (Gánti T: “The Principles of Life”. Oxford University Press,
2003; ChemotonTheory.I.Theoretical foundation offluidmachineries.II.Theory
of living systems. Kluwer Academic/Plenum Publishers 2003. Csendes T.
A simulation study of the chemotron. Kybernetes 1984;13:79–85).
An Advanced Oparin’s Coacervate (кoaцepвaт, Oпapин) would be an imaginary
protobiont, which would engulf either proteobacteria for mitochondrial symbionts
(in animal cells), or cyanobacteria for plastids with eye spot for photosynthesis (in
plantcells).VisitinglecturerNasifNahle,atAguascalientes,Monterrey,Mexicoin
2004, at the Conference of Astrobiology http://biocab.org/Astrobiology.html.
Reverse Transcriptase (D. Baltimore/H.Temin) transforms RNA into complemen-
tary cDNA. mRNA is used as template. The ssDNA strand is made into a dsDNA
strand on a primer by DNA polymerase. Taq (Thermus aquaticus) heat stable
564 Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia
polymerase (K. Mullins) synthesizes complementary DNA strands from primer in
the polymerase chain reaction.
TheExtantDNA/RNAComplexRevertsbacktothePrimordialRNA/DNAComplex.
Predecessor cytogeneticist Barbara McClintock laid down the morphological
foundationsofchromosomescience:deletions,inversions,translocationsofmobile
elements, ring formation, broken ends and fusions, that restructure the genome.
Resurrectionfrom‘genomeshock’.Insertionofrelatedelementsatdistinctlociand
remainingundercoordinatedregulation(McClintockB.Significanceofresponseof
the genome to challenge. Science 1964;226:792–800). Re-emerges the primordial
dependence of DNA on RNA, and on protein enzymes. SINE (short interspersed
nucleotide elements) releasing mRNAs. Retrotransductions of LINEs (long inter-
spersed nucleotide element) consisting of RNA and cDNA molecules.
A combination of exons and introns in inverted terminal repeats. MITE DNA
transposons (miniature inverted-repeat transposable elements). Inter-prokaryotic,
intereukaryotic, including inter-kingdom, horizontal gene transfers. Symbiotic
cellular unisons (cyanobacterial plastids in plant cells; alpha-proteobacterial mito-
chondriainanimalcells).Tertiarysymbiosesindinoflagellates,thusearningenergy
from photosynthesis. Evolution of genomes by whole genome doublings (WGD,
repeatedly so) (Shapiro JA. Mobile DNA and evolution in the 21st century.
MobDNA2019;1.4).Thehumangenomeisinterspersedbytransposableelements
(TE), which are either DNA transposons, or RNA retrotransposons. The retro-
transposonsareSINEs,LINEs,LTRs(longterminalrepeats),andAlus.TEsdictate
the long term evolution of the genome. Satellite S (micro-, or macroS) DNAs are
highcopynumbertandemrepeats.ThesnoRNAs(smallnucleolar)aretheancestors
of the α-Satellate RNAs. Some ncRNAs are expressed from repetitive repRNAs.
Noncoding ncRNAs of highly repetitive regions form a large reservoir capable to
evolve into novel functional RNAs. The 300 bp Alu repeats (Arthrobacter luteus
AluenzymethatcutsDNA)areSINEfamilymemberncRNAs.SINEsderivefrom
tRNAs. SINE’s RNA polymerase III transcribes Alus. Alu sequences remain
embeddedinprotein-codinggenes.SmallnuclearsnRNAsactlikeTEsandendup
as pseudogenes (Matylla-Kulinska K et al Functional repeat-derived RNAs often
originate from retrotransposon-propagated ncRNAs. Wiley Interdiscip Rev RNA
2014;5:591–600). MicroRNAs (miR-661; miR-885-3p) balance p53 and MDM
protein expressions by controlling their mRNAs. In another level, Alus embedded
in the 3’UTR (untranslated region) of mRNAs, as co-recipients of the aligning
microRNAs,mayacceptorrejectalignment(HoffmanYetalmicroRNAsandAlu
elements J Mol Cell Biol 2014;6:192–197). The primate-related SINE-Alu
sequences appeared first in the Branchiostoma amphioxus (Holland LZ A SINE
in the genome of the cephalochordate Int J Biol Sci 2006;2:61–65). In the
Argonaute (AGO)protein family, PIWI proteins bind PIWI-interacting piRNAs (P
element-inducedwimpytestis,drosophila);itisoneofthethreesmallRNAs(micro
miRNA; small interfering siRNA). AGO proteins also bind miRNAs and siRNAs.
PIWI proteins are primarily expressed in the germline, but somatic tissues are not
exemptoftheirpresenceeither;thatincludesstemcells.ThePIWI/piRNApathway
Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia 565
suppresses transposons, thus saving the integrity, and the regulation with chro-
matin,oftheprotein-codinggenes(ManiSR&JulianoCEUntanglingthewebMol
Reprod Dev 2013;80:632–654).
Acholeplasma(Mycoplasma)laidlawiiwasgrownincultureanditsfusogenicphage
particles were purified and concentrated (www.lookfordiagnosis.com). Author’s
first encounter with A. laidlawii occurred in the early 1970s at M.D. Anderson
Hospital, where A. laidlawii was found to have contaminated a human sarcoma
established cell line. The contaminated fluid was transferred to Ferenc Györkey of
thePathologyDepartmentattheVeteransAdministrationHospital,Houston,TXfor
further studies in cell fusion experiments (unpublished). Similar contaminated
human cancer cell cultures were reported from Russia (Polinskaia GG et al
Tsitologiia 2000;42:190–195; 794–801). A swine pathogenic Acholeplasma exists
inHungary(StipkovitsLetalActaVetAcadSciHung1973;23:307–313;361–368;
J Hyg (London) 1974;72:289–296). Cells of the pathogenic PG8 strain of
Acholeplasmalaidlawii(thecausativeagentofphytomycoplasmosisinOryzasativa
L plants infected through their roots) release extracellular membranous vesicles.
These vesicles contained virulence proteins, RNA nucleotide sequences, including
rRNAs(ChernovVM,ChernovaOAetalScientificWorldJ2011;11:1120–1130;
2012;3154–3174; J Proteomics 2014;110:117–128). The presence of rRNAs indi-
cates to this author that the extracellular membranous vesicles are ribosome-like
exosomes. The phenomenon of exosome release is universal in the cellular world.
Observations without actual precise counts indicate that virulent pathogenic or
malignantly transformedcells release excessive numbers of exosomes.Thisauthor
suggestedthat DNA-free butRNA-loaded exosomes(including rRNA) representa
retrogradeevolutionarydescentofthecelltotheprecellulareraofthelivingmatter.
In the RNA World exosome-like units might have populated the Earth. Precellular
ribozyme-armed and readily mutable rRNA-containing ribosome-like units might
have existed with simple ribonucleoproteins (RNP) within (Sinkovics JG Europ J
Microbiol Immunol 2015;5:25–43). Metabolomic analysis shows some unique
differences between A. laidlawii (strain PG-8A) and Mycoplasma pneumoniae in
that, three amino acids (alanine, asparagine, valine) present in M. pneumoniae are
missingfromA.laidlawii.Itispossiblethatalaninisveryrapidlyincorporatedinto
proteinsthroughaminoacyl-tRNAsynthetase,thusapparentlydisappearingfromthe
metabolome. A.laidlawii operates a unique lysine decarboxylase notpossessed by
any other Mycoplasmataceae. In riboflavin biosynthesis, in addition to the cus-
tomary bifunctional riboflavin kinase, only A. laidlawii possessed enzymes for the
conversion of diamino-hydroxyphosphoribosyl-aminopyrimidines (Vanyushkina
AAetalPLoSOne2014;9(3):e89312).Virallyinfected(phage-carrier)JA1strains
of A. laidlawii reveal acute infections with cell lysis, and chronic non-lytic
non-cytocidal infection with rapid growth of infected cells. A. laidlawii has no
bacterialcellwall;itissurroundedbyasinglelipoproteincellmembrane,similarly
to spheroplasts, or to eukaryotic cells of uni- or multicellular hosts (Liss A &
RitterBEJGenMicrobiol1985;131:1713–1718).Afterlysisofthemembranewith
antibody and complement, the remaining cytoplasms were referred to as ghosts
566 Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia
(Brunner H et al Infect Immun 1976; 13:1671–1677), but without stating if the
membrane-freecytoplasmscouldmetabolizeandtowhatextent.Themembrane-free
E.colicytoplasmsobservedbythisauthorwerepresentedasexamplesof“cell-free
living matter”, “plasma” (even though they were lost for further studies in 1956)
(SinkovicsJBiolKözlem(Hungary)1954;2:69–81;1957;5:19–27;ActaMicrobiol
Hung 1957;4;59–75; Die Grundlagen der Virusforschung, Hung Acad Sci, 1956).
However, extracellular E. coli ribosomes remained functional in vitro in the M W
NirenbergandJHMatthaeiexperiments(ProcNatlAcadSciUSA1961;47:1580–
1586; 1588–1602). Now, A. laidlawii exosomes emerge; however, they are
membrane-bound cytoplasmic units (vide supra).The extant Mollicute A. laidlawii
strainsexhibitahighdegreeofgenomicandproteomicdeviationamongthemselves;
the deepest branching member of the clade remains A. laidlawii (Stepens EB et al
Yale J Biol Med 1983;56:729–735; Kube M et al J Mol Microbiol Biotechnol
2014;24:19–35). The ancestors of the unique Mollicute mycoplasma A. laidlawii
anditsfusogenicviruscoexistedwitharchaea(crenarchaea)spheroplasts,ascenario
thatreadilyoffersitselffortheoriesofprimordialcellfusionsthatmighthavecreated
the first eukaryotic cells; a situation possibly amenable to reproduction in the lab-
oratory(Sinkovics JG Acta Microbiol Immunol Hung 2001;48:115–127).
Fusogenic Viruses. Not all phages are lysogenic. An Acholeplasma phage (see
Text) might have been the ancestor of eukaryotic fusogenic viruses, which induce
coalescence of their host cells’ membranes. Of numerous eukaryotic fusogenic
viruses,standouttheMuscervicolorleukemiaretrovirusM813fusingTlymphoma
cells; the EnvV syncytin-producer retroviruses fusing syncytiotrophoblasts of the
placenta; HIV-1 fusion protein fusing infected lymphocytes; influenza viral fusion
peptides fusing lipid bilayer vesicles; parainfluenza and paramyxoviral cell fusion
proteins; corona virus-induced syncytia; measles virus producing multinucleated
giant cells; Sendai virus-fused cells; herpes simplex viral cell-fusogenic glyco-
protein M; env gene/protein-acquiring endogenous retroviruses budding from
human tumor cells (lymphoma, Reed-Sternberg cells, Kaposi sarcoma, adenocar-
cinoma, melanoma) and inducing cell fusions. Virus-producer fused tumor cells
may gain growth advantages; may express new antigenic targets to immune
defensesortoimmunotherapy(seeText).Uponcellularencounters, theidentityor
chemical relatedness of cell membrane or viral capsid/envelope structures leads to
cell fusions (Ogle BM et al Nature Reviews Molecular Cell Biology 2005;6:567–
575). A candidate fusion partner is the ancestral mycoplasma Acholeplasma, and
the primordial mediator is its fusogenic virus (phage) (see in Text).
The much Debated Tree of Life was set into three domains by Ernst Haeckel:
“Monophyletischer Stammbaum der Organismen” consisting of Protista, Plantae
andAnimalia.Extraordinaryacquisitionofgenesthroughhorizontal(lateral)routes
invalidates the evolutionary pathways that were constructed by true vertical
inheritance.AmongBacteria, Mycoplasmataceae viewith Aquifex aeolicus for the
basic position; regression of Mycoplasmataceae from Bacteroides is unacceptable
Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia 567
(Klenk H-P et al J Mol Evol 1999;48;528–541; Woese CR Maniloff J Zablen LB
Proc Natl Acad Sci USA 1980;77:494–498).
After long debates, it has been fully accepted that cyanobacteria entered as endo-
plasmic symbionts of the eukaryotic algae-to-plants lineage; and that ancestral
purple proteobacteria have become the eukaryotic cytoplasmic endosymbiont
mitochondria of animalia.
Archaea are more accurately divided as phyla Crenarchaeota, Euryarchaeota,
Korarchaeota,andNanoarchaeota.Inevolutionaryorder,forthepositionofthefirst
domain, vie the prokaryotes Mycoplasmataceae or Aquifex, with Nanoarchaea.
RecentisolatesincludetheLokiarchaeotaloadedwithgenes,whosesignatureslater
become dominant in the eukaryotic proteomic repertoire (Spang A et al Nature
2015;521;173–179).TheTACKarchaealsuperphylumconsistsofThaumarchaeota/
Aigarchaeota/Crenarchaeota/Korarchaeota existing in sister relationship with
Euryarchaeota, both being ancient carriers of genomes/proteomes that reappear in
eukaryota (Raymann K et al Proc Natl Acad Sci USA 2015;12:6670–6675).
A hyperthermophilic extremophile archaea isolated from the hot springs of the
Yellowstone National Park carries a virus with a circular dsDNA genome, which
encodes elaborate turret-like structures in its capsid. These structures of the
Sulfolobus turreted icosahedral virus re-appear throughout evolution in bacterio-
phages,algalvirusesandadenoviruses.Itsgenemighthaveoriginatedinacommon
ancestorthatexistedbeforethedivisionofthethreedomainsoflife(RiceGetalProc
NatlAcadSciUSA2004;101:7716–20).
Joseph,Rhawn:Geneticsandevolutionofthelifefromotherplanets.JCosmology
2009;1:150–200). In contrast, the present author prefers to envision the origin of
lifeontheancientplanetEarth.Betweenthefirstprotocells,virally-mediatedfusion
of two equal partners: a spheroplast of an archaeon (a crenarchaeota) and a
spheroplastofaprokaryota(amycoplasma),followedbythelaterengulfmentofthe
α-proteobacteriumtobecomethemitochondrium,oracyanobacteriumtobecomea
photosynthetic unit (plastid). Phage-mediated fusions of cell wall-free
mycoplasma-like cells (the Acholeplasma) do occur. The equal fusion partner of
the prokaryota would be a crenarchaeota (both in the form of spheroplasts), but
would they yield to the same fusogenic phage? These basic fundamental experi-
mentsofnaturecouldpossiblybereproducedinalaboratory.Thecandidatefusion
partner archaea might have been thermophilic. Thermophilic archaea populated
(still do) hot submarine vents. Light energy from the Sun does not penetrate the
depths of the seas. There, geothermal radiation provides the energy to anaerobic
photosyntheticpigments(BeattyJTetalProcNatlAcadSciUSA2005;102:9306–
10). Some nanoarchaea (N. equitans and Ignicoccus hospitalis) form unisons
withoutfusion.Suchunisonsareexpectedtohavebeenformedamongthedeepest
branch-offs(StetterKO:Abriefhistory ofthediscoveryofhyperthermophilic life.
Biochem Soc Trans 2013;41:416–429. Jahn U et al Nanoarchaeum equitans and
Ignicoccus hospitalis: New insights into a unique, intimate association of two
568 Appendix1*)ForEssentialInformationVeryWellIllustratedinGoogleandWikipedia
archaea. J Bacteriol 208;190:1743–1750. Podar M et al A genomic analysis of the
archaeal system Ignicoccus hospitalis-Nanoarchaeum equitans. Genome Biol
2008;9(11):R158).Fusedcellsofequalrankscreatedthefirsteukaryote;theunited
large cell was able to engulf single-celled bacteria, which surrendered to
endosymbiosis in a subservient position as mitochondria and plastids. The mito-
chondria transferred most of their genes to the host cell nucleus, but retained the
faculty of the endogenous apoptosis induction in their host cells. The widely
practiced lateral (horizontal) gene transfers between archaea and bacteria (uni-
directional; bidirectional?) resulted in species diversification, but transfer-resistant
macromolecular genes preserved the dominant vertical routes of evolution (Abby
SS et al Proc Natl Acad Sci USA 2012;109:4962–4967).
The Unicellular Ciliate Protozoon, Paramecium tetraurelia, possesses nuclear
dimorphism: a germline genome in its micronucleus (MIC) and a somatic genome
in its macronucleus (MAC). Its cytochrome b5 genes carry out the ubiquitous
electrontransports.Uponitsthreeorfourroundsofwholegenomeduplications,the
largest numbers of reduplicated and retained, and the smallest numbers of lost,
genes are the cytochrome b5 genes (of the whole macronuclear and mitochondrial
genomes consisting of some 40,000 genes). Among others, sequenced were the
tRNA trp and tRNA tyr (tryptophan; tyrosine) genes. The paramecium germ line
nucleusistranscriptionallysilent,andthesomaticmacronucleusistranscriptionally
active. Germ line-specific sequences (internal eliminated sequences, IESs) are
excisedbythethousands,butwithgreat precision(as inotherciliates).One IESis
locatedinanintron.Geneexpressionsarecarriedoutwithextraordinaryreplication
fidelity, especially in their DNA polymerases, resulting in nucleotides conserving
amino acid sites (Sung W et al Proc Natl Acad Sci USA 2012;109;19339–19344;
VayssiéletalNucleicAcidsRes1997;25:1036–1041;WuKJetalGenetMolRes
2013;12:1882–1896).
ConjugatingParamecia.Afterthesexualevent,thenewsomaticMACsubmitsthe
germline MIC to a series of rearrangements. The rearrangements consist of the
precise excision from the diploid germline genome of inserted parasitic DNA
elements.Unique-copyInternalEliminatedSequences(IESs)areexcisedbycertain
long ago inserted, but by now domesticated transposases, such as from the
piggyBack (from cabbage looper moth Trichoplusia ni) to the PiggyMac element.
Targeted are the Tc1/mariner, sardine and anchois transposons. All IESs are rem-
nants of these, or other pre-inserted transposons. Some IES inserts shorten (<159
bp) anddecay.Epigenetic ncRNAs locate thetargets; ncRNAs remainon board to
purify eukaryotic genomes of RNA-to-DNA inserts. Two dinucleotide TA
sequences flank the IES to be excised. Mutated flanking TA dinucleotides with
cis-actingMendelianmutationspreventtheirexcision;otherwisemutationinoneof
the two flanking TA dinucleotides pose an absolute requirement for IES excision.
The Oxytricha genome is heavily infested by inserted transposons. The endonu-
clease required for the cleavage of the Oxytricha genome is a transposase derived
from its germline TBE (telomere-bearing elements) transposons. The piggyback